Prioritization schema for immunotherapy clinical trials in glioblastoma

References

• Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352:987-96; PMID:15758009; http://dx.doi.org/10.1056/NEJMoa043330
   PubMed Web of Science ®Google Scholar
• GBM AGILE (An Adaptive, Global, Innovative Learning Environment) to Implement Unprecedented International Clinical Trial. National Biomarker Development Alliance 2015; http://nbdabiomarkers.org/gbm-agile
   Google Scholar
• Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009; 151:264-9, W64; PMID:19622511; http://dx.doi.org/10.7326/0003-4819-151-4-200908180-00135
   PubMed Web of Science ®Google Scholar
• Heimberger AB, Crotty LE, Archer GE, Hess KR, Wikstrand CJ, Friedman AH, Friedman HS, Bigner DD, Sampson JH. Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res 2003; 9:4247-54; PMID:14519652
   PubMed Web of Science ®Google Scholar
• Sampson JH, Crotty LE, Lee S, Archer GE, Ashley DM, Wikstrand CJ, Hale LP, Small C, Dranoff G, Friedman AH et al. Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors. Proc Natl Acad Sci U S A 2000; 97:7503-8; PMID:10852962; http://dx.doi.org/10.1073/pnas.130166597
   PubMed Web of Science ®Google Scholar
• Murat A, Migliavacca E, Gorlia T, Lambiv WL, Shay T, Hamou MF, de Tribolet N, Regli L, Wick W, Kouwenhoven MC et al. Stem cell-related “self-renewal” signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol 2008; 26:3015-24; PMID:18565887; http://dx.doi.org/10.1200/JCO.2007.15.7164
   PubMed Web of Science ®Google Scholar
• Wei J, Barr J, Kong LY, Wang Y, Wu A, Sharma AK, Gumin J, Henry V, Colman H, Priebe W et al. Glioblastoma cancer-initiating cells inhibit T-cell proliferation and effector responses by the signal transducers and activators of transcription 3 pathway. Mol Cancer Ther 2010; 9:67-78; PMID:20053772; http://dx.doi.org/10.1158/1535-7163.MCT-09-0734
   PubMed Web of Science ®Google Scholar
• Wainwright DA, Chang AL, Dey M, Balyasnikova IV, Kim C, Tobias AL, Cheng Y, Kim J, Qiao J, Zhang L et al. Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4 and PD-L1 in mice with brain tumors. Clin Cancer Res 2014; 20:5290-301; PMID:24691018; http://dx.doi.org/10.1158/1078-0432.CCR-14-0514
   PubMed Web of Science ®Google Scholar
• Berghoff AS, Kiesel B, Widhalm G, Rajky O, Ricken G, Wohrer A, Dieckmann K, Filipits M, Brandstetter A, Weller M et al. Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma. Neuro Oncol 2015; 17:1064-75; PMID:25355681; http://dx.doi.org/10.1093/neuonc/nou307
   PubMed Web of Science ®Google Scholar
• Nduom EK, Wei J, Yaghi NK, Huang N, Kong LY, Gabrusiewicz K, Ling X, Zhou S, Ivan C, Chen JQ et al. PD-L1 expression and prognostic impact in glioblastoma. Neuro Oncol In Press.
   Google Scholar
• Ali HR, Glont SE, Blows FM, Provenzano E, Dawson SJ, Liu B, Hiller L, Dunn J, Poole CJ, Bowden S et al. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol 2015; 26:1488-93; PMID:25897014; http://dx.doi.org/10.1093/annonc/mdv518.22
   PubMed Web of Science ®Google Scholar
• D'Angelo SP, Shoushtari AN, Agaram NP, Kuk D, Qin LX, Carvajal RD, Dickson MA, Gounder M, Keohan ML, Schwartz GK et al. Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment. Hum Pathol 2015; 46:357-65; PMID:25540867; http://dx.doi.org/10.1016/j.humpath.2014.11.001
   PubMed Web of Science ®Google Scholar
• Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, Parmiani G, Tosti G, Kirkwood JM, Hoos A et al. Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group. J Clin Oncol 2008; 26:955-62; PMID:18281670; http://dx.doi.org/10.1200/JCO.2007.11.9941
   PubMed Web of Science ®Google Scholar
• Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, Mulders P, Zielinski H, Hoos A, Teofilovici F et al. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet 2008; 372:145-54; PMID:18602688; http://dx.doi.org/10.1016/S0140-6736(08)60697-2
   PubMed Web of Science ®Google Scholar
• Cobbs C, Harkins L, Samanta M, Gillespie G, Bharara S, King P, Nabors L, Cobbs C, Britt W. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res 2002; 62:3347-50; PMID:12067971
   PubMed Web of Science ®Google Scholar
• Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, Sampson JH. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol 2008; 10:10-8; PMID:17951512; http://dx.doi.org/10.1215/15228517-2007-035
   PubMed Web of Science ®Google Scholar
• Ranganathan P, Clark PA, Kuo JS, Salamat MS, Kalejta RF. Significant association of multiple human cytomegalovirus genomic Loci with glioblastoma multiforme samples. J Virol 2012; 86:854-64; PMID:22090104; http://dx.doi.org/10.1128/JVI.06097-11
   PubMed Web of Science ®Google Scholar
• Lawler SE. Cytomegalovirus and glioblastoma; controversies and opportunities. J Neurooncol 2015; 123:465-71; PMID:25682092; http://dx.doi.org/10.1007/s11060-015-1734-0
   PubMed Web of Science ®Google Scholar
• Wick W, Platten M. CMV infection and glioma, a highly controversial concept struggling in the clinical arena. Neuro Oncol 2014; 16:332-3; PMID:24523454; http://dx.doi.org/10.1093/neuonc/nou002
   PubMed Web of Science ®Google Scholar
• Cobbs CS, Soroceanu L, Denham S, Zhang W, Kraus MH. Modulation of oncogenic phenotype in human glioma cells by cytomegalovirus IE1-mediated mitogenicity. Cancer Res 2008; 68:724-30; PMID:18245472; http://dx.doi.org/10.1158/0008-5472.CAN-07-2291
   PubMed Web of Science ®Google Scholar
• Stragliotto G, Rahbar A, Solberg NW, Lilja A, Taher C, Orrego A, Bjurman B, Tammik C, Skarman P, Peredo I et al. Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: a randomized, double-blind, hypothesis-generating study. Int J Cancer 2013; 133:1204-13; PMID:23404447; http://dx.doi.org/10.1002/ijc.28111
   PubMed Web of Science ®Google Scholar
• Mitchell DA, Batich KA, Gunn MD, Huang MN, Sanchez-Perez L, Nair SK, Congdon KL, Reap EA, Archer GE, Desjardins A et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature 2015; 519:366-9; PMID:25762141; http://dx.doi.org/10.1038/nature14320
   PubMed Web of Science ®Google Scholar
• Moscatello DK, Holgado-Madruga M, Godwin AK, Ramirez G, Gunn G, Zoltick PW, Biegel JA, Hayes RL, Wong AJ. Frequent expression of a mutant epidermal growth factor receptor in multiple human tumors. Cancer Research 1995; 55:5536-9; PMID:7585629
   PubMed Web of Science ®Google Scholar
• Shinojima N, Tada K, Shiraishi S, Kamiryo T, Kochi M, Nakamura H, Makino K, Saya H, Hirano H, Kuratsu J et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res 2003; 63:6962-70; PMID:14583498
   PubMed Web of Science ®Google Scholar
• Wikstrand CJ, McLendon RE, Friedman AH, Bigner DD. Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII. Cancer Res 1997; 57:4130-40; PMID:9307304
   PubMed Web of Science ®Google Scholar
• Heimberger AB, Hlatky R, Suki D, Yang D, Weinberg J, Gilbert M, Sawaya R, Aldape K. Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res 2005; 11:1462-6; PMID:15746047; http://dx.doi.org/10.1158/1078-0432.CCR-04-1737
   PubMed Web of Science ®Google Scholar
• Sampson JH, Heimberger AB, Archer GE, Aldape KD, Friedman AH, Friedman HS, Gilbert MR, Herndon JE, 2nd, McLendon RE, Mitchell DA et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol 2010; 28:4722-9; PMID:20921459; http://dx.doi.org/10.1200/JCO.2010.28.6963
   PubMed Web of Science ®Google Scholar
• Reardon DA, Schuster JM, Tran DD, Fink KL, Nabors LB, Li G, Bota DA, Lukas RV, Desjardins A, Ashby LS et al. 107 ReACT: Overall Survival From a Randomized Phase II Study of Rindopepimut (CDX-110) Plus Bevacizumab in Relapsed Glioblastoma. Neurosurgery 2015; 62 Suppl 1:198-9; http://dx.doi.org/10.1227/01.neu.0000467069.86811.3f
   Google Scholar
• Schuster J, Lai RK, Recht LD, Reardon DA, Paleologos NA, Groves MD, Mrugala MM, Jensen R, Baehring JM, Sloan A et al. A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study. Neuro Oncol 2015; 17:854-61; PMID:25586468; http://dx.doi.org/10.1093/neuonc/nou348
   PubMed Web of Science ®Google Scholar
• Hunn MK, Bauer E, Wood CE, Gasser O, Dzhelali M, Ancelet LR, Mester B, Sharples KJ, Findlay MP, Hamilton DA et al. Dendritic cell vaccination combined with temozolomide retreatment: results of a phase I trial in patients with recurrent glioblastoma multiforme. J Neurooncol 2015; 121:319-29; PMID:25366363; http://dx.doi.org/10.1007/s11060-014-1635-7
   PubMed Web of Science ®Google Scholar
• Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol 2011; 29:330-6; PMID:21149657; http://dx.doi.org/10.1200/JCO.2010.30.7744
   PubMed Web of Science ®Google Scholar
• Ardon H, Van Gool S, Lopes IS, Maes W, Sciot R, Wilms G, Demaerel P, Bijttebier P, Claes L, Goffin J et al. Integration of autologous dendritic cell-based immunotherapy in the primary treatment for patients with newly diagnosed glioblastoma multiforme: a pilot study. J Neurooncol 2010; 99:261-72; PMID:20146084; http://dx.doi.org/10.1007/s11060-010-0131-y
   PubMed Web of Science ®Google Scholar
• Ardon H, Van Gool SW, Verschuere T, Maes W, Fieuws S, Sciot R, Wilms G, Demaerel P, Goffin J, Van Calenbergh F et al. Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial. Cancer Immunol Immun 2012 Nov; 61(11):2033-44; PMID:22527250; http://dx.doi.org/10.1007/s00262-012-1261-1.
   PubMed Web of Science ®Google Scholar
• Everson RG, Jin RM, Wang X, Safaee M, Scharnweber R, Lisiero DN, Soto H, Liau LM, Prins RM. Cytokine responsiveness of CD8(+) T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients. J Immunother Cancer 2014; 2:10; PMID:24883189; http://dx.doi.org/10.1186/2051-1426-2-10
   PubMedGoogle Scholar
• Liau LM, Prins RM, Kiertscher SM, Odesa SK, Kremen TJ, Giovannone AJ, Lin JW, Chute DJ, Mischel PS, Cloughesy TF et al. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res 2005; 11:5515-25; PMID:16061868; http://dx.doi.org/10.1158/1078-0432.CCR-05-0464
   PubMed Web of Science ®Google Scholar
• Yu JS, Wheeler CJ, Zeltzer PM, Ying H, Finger DN, Lee PK, Yong WH, Incardona F, Thompson RC, Riedinger MS et al. Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Research 2001; 61:842-7; PMID:11221866
   PubMed Web of Science ®Google Scholar
• Nair SK, De Leon G, Boczkowski D, Schmittling R, Xie W, Staats J, Liu R, Johnson LA, Weinhold K, Archer GE et al. Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells. Clin Cancer Res 2014; 20:2684-94; PMID:24658154; http://dx.doi.org/10.1158/1078-0432.CCR-13-3268
   PubMed Web of Science ®Google Scholar
• Prins RM, Cloughesy TF, Liau LM. Cytomegalovirus immunity after vaccination with autologous glioblastoma lysate. N Engl J Med 2008; 359:539-41; PMID:18669440; http://dx.doi.org/10.1056/NEJMc0804818
   PubMed Web of Science ®Google Scholar
• Yu P, Lee Y, Liu W, Chin RK, Wang J, Wang Y, Schietinger A, Philip M, Schreiber H, Fu YX. Priming of naive T cells inside tumors leads to eradication of established tumors.[see comment]. Nat Immunol 2004; 5:141-9; PMID:14704792; http://dx.doi.org/10.1038/ni1029
   PubMed Web of Science ®Google Scholar
• Yu J, Liu G, Ying H, Yong W, Black K, Wheeler CJ. Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res 2004; 64:4973-9; PMID:15256471; http://dx.doi.org/10.1158/0008-5472.CAN-03-3505
   PubMed Web of Science ®Google Scholar
• Kjellman C, Olofsson SP, Hansson O, Von Schantz T, Lindvall M, Nilsson I, Salford LG, Sjogren HO, Widegren B. Expression of TGF-beta isoforms, TGF-beta receptors, and SMAD molecules at different stages of human glioma. Int J Cancer 2000; 89:251-8; PMID:10861501; http://dx.doi.org/10.1002/1097-0215(20000520)89:3%3c251::AID-IJC7%3e3.0.CO;2-5
   PubMed Web of Science ®Google Scholar
• Maxwell M, Galanopoulos T, Neville-Golden J, Antoniades HN. Effect of the expression of transforming growth factor-beta 2 in primary human glioblastomas on immunosuppression and loss of immune surveillance. JNeurosurg 1992; 76:799-804; http://dx.doi.org/10.3171/jns.1992.76.5.0799
   Web of Science ®Google Scholar
• Jachimczak P, Bogdahn U, Schneider J, Behl C, Meixensberger J, Apfel, R, Dorries R, Schlingensiepen KH, Brysch W. The effect of transforming growth factor-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma. JNeurosurg 1993; 78:944-51; http://dx.doi.org/10.3171/jns.1993.78.6.0944
   Web of Science ®Google Scholar
• Jachimczak P, Hessdorfer B, Fabel-Schulte K, Wismeth C, Brysch W, Schlingensiepen KH, Bauer A, Blesch A, Bogdahn U. Transforming growth factor-beta-mediated autocrine growth regulation of gliomas as detected with phosphorothioate antisense oligonucleotides. Int J Cancer 1996; 65:332-7; PMID:8575854; http://dx.doi.org/10.1002/(SICI)1097-0215(19960126)65:3%3c332::AID-IJC10%3e3.0.CO;2-C
   PubMed Web of Science ®Google Scholar
• Hau P, Jachimczak P, Schlingensiepen R, Schulmeyer F, Jauch T, Steinbrecher A, Brawanski A, Proescholdt M, Schlaier J, Buchroithner J et al. Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies. Oligonucleotides 2007; 17:201-12; PMID:17638524; http://dx.doi.org/10.1089/oli.2006.0053
   PubMed Web of Science ®Google Scholar
• Bogdahn U, Hau P, Stockhammer G, Venkataramana NK, Mahapatra AK, Suri A, Balasubramaniam A, Nair S, Oliushine V, Parfenov V et al. Targeted therapy for high-grade glioma with the TGF-beta2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro Oncol 2011; 13:132-42; PMID:20980335; http://dx.doi.org/10.1093/neuonc/noq142
   PubMed Web of Science ®Google Scholar
• Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC et al. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. N Engl J Med 2010; 363:711-23; PMID:20525992; http://dx.doi.org/10.1056/NEJMoa1003466
   PubMed Web of Science ®Google Scholar
• Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369:134-44; PMID:23724846; http://dx.doi.org/10.1056/NEJMoa1305133
   PubMed Web of Science ®Google Scholar
• Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu WJ, Gangadhar TC et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014; 384:1109-17; PMID:25034862; http://dx.doi.org/10.1016/S0140-6736(14)60958-2
   PubMed Web of Science ®Google Scholar
• Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014; 32:1020-30; PMID:24590637; http://dx.doi.org/10.1200/JCO.2013.53.0105
   PubMed Web of Science ®Google Scholar
• Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015; 373:23-34; PMID:26027431; http://dx.doi.org/10.1056/NEJMoa1504030
   PubMed Web of Science ®Google Scholar
• Heimberger AB, Abou-Ghazal M, Reina-Ortiz C, Yang DS, Sun W, Qiao W, Hiraoka N, Fuller GN. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin Cancer Res 2008; 14:5166-72; PMID:18698034; http://dx.doi.org/10.1158/1078-0432.CCR-08-0320
   PubMed Web of Science ®Google Scholar
• Mitchell DA, Cui X, Schmittling RJ, Sanchez-Perez L, Snyder DJ, Congdon KL, Archer GE, Desjardins A, Friedman AH, Friedman HS et al. Monoclonal antibody blockade of IL-2 receptor alpha during lymphopenia selectively depletes regulatory T cells in mice and humans. Blood 2011; 118:3003-12; PMID:21768296; http://dx.doi.org/10.1182/blood-2011-02-334565
   PubMed Web of Science ®Google Scholar
• Sampson JH, Schmittling RJ, Archer GE, Congdon KL, Nair SK, Reap EA, Desjardins A, Friedman AH, Friedman HS, Herndon JE, 2nd et al. A pilot study of IL-2Ralpha blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma. PLoS One 2012; 7:e31046; PMID:22383993; http://dx.doi.org/10.1371/journal.pone.0031046
   PubMed Web of Science ®Google Scholar
• Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, Stefoski D, Robinson R, Riester K, Rana J et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet 2013; 381:2167-75; PMID:23562009; http://dx.doi.org/10.1016/S0140-6736(12)62190-4
   PubMed Web of Science ®Google Scholar
• Hussain SF, Yang D, Suki D, Aldape K, Grimm E, Heimberger AB. The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro Oncol 2006; 8:261-79; PMID:16775224; http://dx.doi.org/10.1215/15228517-2006-008
   PubMed Web of Science ®Google Scholar
• Komohara Y, Ohnishi K, Kuratsu J, Takeya M. Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. J Pathol 2008; 216:15-24; PMID:18553315; http://dx.doi.org/10.1002/path.2370
   PubMed Web of Science ®Google Scholar
• Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, Olson OC, Quick ML, Huse JT, Teijeiro V et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med 2013; 19:1264-72; PMID:24056773; http://dx.doi.org/10.1038/nm.3337
   PubMed Web of Science ®Google Scholar
• Ries CH, Hoves S, Cannarile MA, Ruttinger D. CSF-1/CSF-1R targeting agents in clinical development for cancer therapy. Curr Opin Pharmacol 2015; 23:45-51; PMID:26051995; http://dx.doi.org/10.1016/j.coph.2015.05.008
   PubMed Web of Science ®Google Scholar
• von Tresckow B, Morschhauser F, Ribrag V, Topp MS, Chien C, Seetharam S, Aquino R, Kotoulek S, de Boer CJ, Engert A. An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma. Clin Cancer Res 2015; 21:1843-50; PMID:25628399; http://dx.doi.org/10.1158/1078-0432.CCR-14-1845
   PubMed Web of Science ®Google Scholar
• Crough T, Beagley L, Smith C, Jones L, Walker DG, Khanna R. Ex vivo functional analysis, expansion and adoptive transfer of cytomegalovirus-specific T-cells in patients with glioblastoma multiforme. Immunol Cell Biol 2012; 90:872-80; PMID:22508289; http://dx.doi.org/10.1038/icb.2012.19
   PubMed Web of Science ®Google Scholar
• Dillman RO, Duma CM, Ellis RA, Cornforth AN, Schiltz PM, Sharp SL, DePriest MC. Intralesional lymphokine-activated killer cells as adjuvant therapy for primary glioblastoma. J Immunother 2009; 32:914-9; PMID:19816190; http://dx.doi.org/10.1097/CJI.0b013e3181b2910f
   PubMed Web of Science ®Google Scholar
• Dillman RO, Duma CM, Schiltz PM, DePriest C, Ellis RA, Okamoto K, Beutel LD, De Leon C, Chico S. Intracavitary placement of autologous lymphokine-activated killer (LAK) cells after resection of recurrent glioblastoma. J Immunother 2004; 27:398-404; PMID:15314549; http://dx.doi.org/10.1097/00002371-200409000-00009
   PubMed Web of Science ®Google Scholar
• Ishikawa E, Tsuboi K, Saijo K, Harada H, Takano S, Nose T, Ohno T. Autologous natural killer cell therapy for human recurrent malignant glioma. Anticancer Res 2004; 24:1861-71; PMID:15274367
   PubMed Web of Science ®Google Scholar
• Schuessler A, Smith C, Beagley L, Boyle GM, Rehan S, Matthews K, Jones L, Crough T, Dasari V, Klein K et al. Autologous T-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma. Cancer Res 2014; 74:3466-76; PMID:24795429; http://dx.doi.org/10.1158/0008-5472.CAN-14-0296
   PubMed Web of Science ®Google Scholar
• Choi BD, Suryadevara CM, Gedeon PC, Herndon JE, 2nd, Sanchez-Perez L, Bigner DD, Sampson JH. Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma. J Clin Neurosci 2014; 21:189-90; PMID:24054399; http://dx.doi.org/10.1016/j.jocn.2013.03.012
   PubMed Web of Science ®Google Scholar
• Miao H, Choi BD, Suryadevara CM, Sanchez-Perez L, Yang S, De Leon G, Sayour EJ, McLendon R, Herndon JE, 2nd, Healy P et al. EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma. PLoS One 2014; 9:e94281; PMID:24722266; http://dx.doi.org/10.1371/journal.pone.0094281
   PubMed Web of Science ®Google Scholar
• Johnson LA, Scholler J, Ohkuri T, Kosaka A, Patel PR, McGettigan SE, Nace AK, Dentchev T, Thekkat P, Loew A et al. Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Sci Transl Med 2015; 7:275ra22; PMID:25696001; http://dx.doi.org/10.1126/scitranslmed.aaa4963
   PubMed Web of Science ®Google Scholar
• Ohno M, Ohkuri T, Kosaka A, Tanahashi K, June CH, Natsume A, Okada H. Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts. J Immunother Cancer 2013; 1:21; PMID:24829757; http://dx.doi.org/10.1186/2051-1426-1-21
   PubMedGoogle Scholar
• Brown CE, Badie B, Barish ME, Weng L, Ostberg JR, Chang WC, Naranjo A, Starr R, Wagner J, Wright C et al. Bioactivity and Safety of IL13Ralpha2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. Clin Cancer Res 2015; 21(18):4062-72; PMID:26059190; http://dx.doi.org/10.1158/1078-0432.CCR-15-0428.
   PubMed Web of Science ®Google Scholar
• Caruso HG, Hurton LV, Najjar A, Rushworth D, Ang S, Olivares S, Mi T, Switzer K, Singh H, Huls H, et al. Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity. Cancer Res 2015; 75(17):3505–18; PMID:26330164; http://dx.doi.org/10.1158/0008-5472.CAN-15-0139.
   PubMed Web of Science ®Google Scholar
• Abou-Ghazal M, Yang DS, Qiao W, Reina-Ortiz C, Wei J, Kong LY, Fuller GN, Hiraoka N, Priebe W, Sawaya R et al. The incidence, correlation with tumor-infiltrating inflammation, and prognosis of phosphorylated STAT3 expression in human gliomas. Clin Cancer Res 2008; 14:8228-35; PMID:19088040; http://dx.doi.org/10.1158/1078-0432.CCR-08-1329
   PubMed Web of Science ®Google Scholar
• Huang S. Regulation of metastases by signal transducer and activator of transcription 3 signaling pathway: clinical implications. Clin Cancer Res 2007; 13:1362-6; PMID:17332277; http://dx.doi.org/10.1158/1078-0432.CCR-06-2313
   PubMed Web of Science ®Google Scholar
• Yu H, Jove R. The STATs of cancer–new molecular targets come of age. Nat Rev Cancer 2004; 4:97-105; PMID:14964307; http://dx.doi.org/10.1038/nrc1275
   PubMed Web of Science ®Google Scholar
• Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007; 7:41-51; PMID:17186030; http://dx.doi.org/10.1038/nri1995
   PubMed Web of Science ®Google Scholar
• Kong LY, Wei J, Sharma AK, Barr J, Abou-Ghazal MK, Fokt I, Weinberg J, Rao G, Grimm E, Priebe W et al. A novel phosphorylated STAT3 inhibitor enhances T cell cytotoxicity against melanoma through inhibition of regulatory T cells. Cancer Immunol Immunother 2009; 58:1023-32; PMID:19002459; http://dx.doi.org/10.1007/s00262-008-0618-y
   PubMed Web of Science ®Google Scholar
• Nefedova Y, Huang M, Kusmartsev S, Bhattacharya R, Cheng P, Salup R, Jove R, Gabrilovich D. Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J Immunol 2004; 172:464-74; PMID:14688356; http://dx.doi.org/10.4049/jimmunol.172.1.464
   PubMed Web of Science ®Google Scholar
• Nefedova Y, Nagaraj S, Rosenbauer A, Muro-Cacho C, Sebti SM, Gabrilovich DI. Regulation of dendritic cell differentiation and antitumor immune response in cancer by pharmacologic-selective inhibition of the janus-activated kinase 2/signal transducers and activators of transcription 3 pathway. Cancer Res 2005; 65:9525-35; PMID:16230418; http://dx.doi.org/10.1158/0008-5472.CAN-05-0529
   PubMed Web of Science ®Google Scholar
• Sherry MM, Reeves A, Wu JK, Cochran BH. STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells. Stem Cells 2009; 27:2383-92; PMID:19658181; http://dx.doi.org/10.1002/stem.185
   PubMed Web of Science ®Google Scholar
• Wei J, Barr J, Kong LY, Wang Y, Wu A, Sharma AK, Gumin J, Henry V, Colman H, Sawaya R et al. Glioma-associated cancer-initiating cells induce immunosuppression. Clin Cancer Res 2010; 16:461-73; PMID:20068105; http://dx.doi.org/10.1158/1078-0432.CCR-09-1983
   PubMed Web of Science ®Google Scholar
• Ashizawa T, Miyata H, Iizuka A, Komiyama M, Oshita C, Kume A, Nogami M, Yagoto M, Ito I, Oishi T et al. Effect of the STAT3 inhibitor STX-0119 on the proliferation of cancer stem-like cells derived from recurrent glioblastoma. Int J Oncol 2013; 43:219-27; PMID:23612755; http://dx.doi.org/10.3892/ijo.2013.1916
   PubMed Web of Science ®Google Scholar
• Plimack ER, Lorusso PM, McCoon P, Tang W, Krebs AD, Curt G, Eckhardt SG. AZD1480: a phase I study of a novel JAK2 inhibitor in solid tumors. Oncologist 2013; 18:819-20; PMID:23847256; http://dx.doi.org/10.1634/theoncologist.2013-0198
   PubMed Web of Science ®Google Scholar
• Zielinski R, Rusin A, Madden T, Conrad C, Johansen M, Fokt I, Skora S, Jayakumar A, Heimberger A, Priebe W. Abstract 4540:Development of orally bioavailable formulatin of WP1066 and its evaluation in vivo. AACR 106th Annual Meeting. Philadelphia, PA: Cancer Res, 2015.
   Google Scholar
• Choi BD, Gedeon PC, Sanchez-Perez L, Bigner DD, Sampson JH. Regulatory T cells are redirected to kill glioblastoma by an EGFRvIII-targeted bispecific antibody. Oncoimmunology 2013; 2:e26757; PMID:24475376; http://dx.doi.org/10.4161/onci.26757
   PubMed Web of Science ®Google Scholar
• Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360:765-73; PMID:19228619; http://dx.doi.org/10.1056/NEJMoa0808710
   PubMed Web of Science ®Google Scholar
• Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321:1807-12; PMID:18772396; http://dx.doi.org/10.1126/science.1164382
   PubMed Web of Science ®Google Scholar
• Pellegatta S, Valletta L, Corbetta C, Patane M, Zucca I, Riccardi Sirtori F, Bruzzone MG, Fogliatto G, Isacchi A, Pollo B et al. Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma. Acta neuropathologica communications 2015; 3:4; PMID:25849072; http://dx.doi.org/10.1186/s40478-014-0180-0
   PubMed Web of Science ®Google Scholar
• Schumacher T, Bunse L, Pusch S, Sahm F, Wiestler B, Quandt J, Menn O, Osswald M, Oezen I, Ott M et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 2014; 512:324-7; PMID:25043048; http://dx.doi.org/10.1038/nature13387
   PubMed Web of Science ®Google Scholar
• Hellums EK, Markert JM, Parker JN, He B, Perbal B, Roizman B, Whitley RJ, Langford CP, Bharara S, Gillespie GY. Increased efficacy of an interleukin-12-secreting herpes simplex virus in a syngeneic intracranial murine glioma model. Neuro Oncol 2005; 7:213-24; PMID:16053696; http://dx.doi.org/10.1215/S1152851705000074
   PubMed Web of Science ®Google Scholar
• Markert JM, Cody JJ, Parker JN, Coleman JM, Price KH, Kern ER, Quenelle DC, Lakeman AD, Schoeb TR, Palmer CA et al. Preclinical evaluation of a genetically engineered herpes simplex virus expressing interleukin-12. J Virol 2012; 86:5304-13; PMID:22379082; http://dx.doi.org/10.1128/JVI.06998-11
   PubMed Web of Science ®Google Scholar
• Parker JN, Gillespie GY, Love CE, Randall S, Whitley RJ, Markert JM. Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors. Proc Natl Acad Sci U S A 2000; 97:2208-13; PMID:10681459; http://dx.doi.org/10.1073/pnas.040557897
   PubMed Web of Science ®Google Scholar
• Wakimoto H, Kesari S, Farrell CJ, Curry WT, Jr., Zaupa C, Aghi M, Kuroda T, Stemmer-Rachamimov A, Shah K, Liu TC et al. Human glioblastoma-derived cancer stem cells: establishment of invasive glioma models and treatment with oncolytic herpes simplex virus vectors. Cancer Res 2009; 69:3472-81; PMID:19351838; http://dx.doi.org/10.1158/0008-5472.CAN-08-3886
   PubMed Web of Science ®Google Scholar
• Roth JC, Cassady KA, Cody JJ, Parker JN, Price KH, Coleman JM, Peggins JO, Noker PE, Powers NW, Grimes SD et al. Evaluation of the safety and biodistribution of M032, an attenuated herpes simplex virus type 1 expressing hIL-12, after intracerebral administration to aotus nonhuman primates. Human gene therapy Clinical development 2014; 25:16-27; PMID:24649838; http://dx.doi.org/10.1089/humc.2013.201
   PubMed Web of Science ®Google Scholar
• John J, Nemunaitis GPL, Haythem A, Lebel F, Barrett JA, Reed T, Krishnan S, Lewis J, Norton L. Ad-RTS-hIL-12 + veledimex regulation of IL-12 expression in advanced Breast Cancer (BC) and Melanoma Patients. AACR Annual Meeting 2014, 2014
   Google Scholar
• Ali S, King GD, Curtin JF, Candolfi M, Xiong W, Liu C, Puntel M, Cheng Q, Prieto J, Ribas A et al. Combined immunostimulation and conditional cytotoxic gene therapy provide long-term survival in a large glioma model. Cancer Res 2005; 65:7194-204; PMID:16103070; http://dx.doi.org/10.1158/0008-5472.CAN-04-3434
   PubMed Web of Science ®Google Scholar
• Curtin JF, Liu N, Candolfi M, Xiong W, Assi H, Yagiz K, Edwards MR, Michelsen KS, Kroeger KM, Liu C et al. HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med 2009; 6:e10; PMID:19143470; http://dx.doi.org/10.1371/journal.pmed.1000010
   PubMed Web of Science ®Google Scholar
• Tran TT, Uhl M, Ma JY, Janssen L, Sriram V, Aulwurm S, Kerr I, Lam A, Webb HK, Kapoun AM et al. Inhibiting TGF-beta signaling restores immune surveillance in the SMA-560 glioma model. Neuro Oncol 2007; 9:259-70; PMID:17522330; http://dx.doi.org/10.1215/15228517-2007-010
   PubMed Web of Science ®Google Scholar
• Yu J, Wheeler C, Zeltzer P, Ying H, Finger D, Lee P, Yong W, Incardona F, Thompson R, Riedinger M et al. Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res 2001; 61:842-7; PMID:11221866
   PubMed Web of Science ®Google Scholar
• Zhu X, Fallert-Junecko BA, Fujita M, Ueda R, Kohanbash G, Kastenhuber ER, McDonald HA, Liu Y, Kalinski P, Reinhart TA et al. Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-alpha and IFN-gamma dependent manners. Cancer Immunol Immunother 2010; 59:1401-9; PMID:20549206; http://dx.doi.org/10.1007/s00262-010-0876-3
   PubMed Web of Science ®Google Scholar
• Zhu X, Nishimura F, Sasaki K, Fujita M, Dusak JE, Eguchi J, Fellows-Mayle W, Storkus WJ, Walker PR, Salazar AM et al. Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor models. J Transl Med 2007; 5:10; PMID:17295916; http://dx.doi.org/10.1186/1479-5876-5-10
   PubMed Web of Science ®Google Scholar
• Butowski N, Chang SM, Junck L, DeAngelis LM, Abrey L, Fink K, Cloughesy T, Lamborn KR, Salazar AM, Prados MD. A phase II clinical trial of poly-ICLC with radiation for adult patients with newly diagnosed supratentorial glioblastoma: a North American Brain Tumor Consortium (NABTC01-05). J Neurooncol 2009; 91:175-82; PMID:18797818; http://dx.doi.org/10.1007/s11060-008-9693-3
   PubMed Web of Science ®Google Scholar
• Carpentier A, Metellus P, Ursu R, Zohar S, Lafitte F, Barrie M, Meng Y, Richard M, Parizot C, Laigle-Donadey F et al. Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study. Neuro Oncol 2010; 12:401-8; PMID:20308317; http://dx.doi.org/10.1093/neuonc/nop047
   PubMed Web of Science ®Google Scholar
• Rosenfeld MR, Chamberlain MC, Grossman SA, Peereboom DM, Lesser GJ, Batchelor TT, Desideri S, Salazar AM, Ye X. A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma. Neuro Oncol 2010; 12:1071-7; PMID:20615924; http://dx.doi.org/10.1093/neuonc/noq071
   PubMed Web of Science ®Google Scholar
• Bloch O, Crane CA, Fuks Y, Kaur R, Aghi MK, Berger MS, Butowski NA, Chang SM, Clarke JL, McDermott MW et al. Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial. Neuro Oncol 2014; 16:274-9; PMID:24335700; http://dx.doi.org/10.1093/neuonc/not203
   PubMed Web of Science ®Google Scholar
• Crane CA, Han SJ, Ahn B, Oehlke J, Kivett V, Fedoroff A, Butowski N, Chang SM, Clarke J, Berger MS et al. Individual patient-specific immunity against high-grade glioma after vaccination with autologous tumor derived peptides bound to the 96 KD chaperone protein. Clin Cancer Res 2013; 19:205-14; PMID:22872572; http://dx.doi.org/10.1158/1078-0432.CCR-11-3358
   PubMed Web of Science ®Google Scholar
• Ramalingam S, Crawford J, Chang A, Manegold C, Perez-Soler R, Douillard JY, Thatcher N, Barlesi F, Owonikoko T, Wang Y et al. Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial). Ann Oncol 2013; 24:2875-80; PMID:24050956; http://dx.doi.org/10.1093/annonc/mdt371
   PubMed Web of Science ®Google Scholar
• Schadendorf D, Ugurel S, Schuler-Thurner B, Nestle FO, Enk A, Brocker EB, Grabbe S, Rittgen W, Edler L, Sucker A et al. Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Ann Oncol 2006; 17:563-70; PMID:16418308; http://dx.doi.org/10.1093/annonc/mdj138
   PubMed Web of Science ®Google Scholar
• Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006; 24:3089-94; PMID:16809734; http://dx.doi.org/10.1200/JCO.2005.04.5252
   PubMed Web of Science ®Google Scholar
• Fletcher M, Ramirez ME, Sierra RA, Raber P, Thevenot P, Al-Khami AA, Sanchez-Pino D, Hernandez C, Wyczechowska DD, Ochoa AC et al. l-Arginine depletion blunts antitumor T-cell responses by inducing myeloid-derived suppressor cells. Cancer Res 2015; 75:275-83; PMID:25406192; http://dx.doi.org/10.1158/0008-5472.CAN-14-1491
   PubMed Web of Science ®Google Scholar
• Lieberman MD, Nishioka K, Redmond HP, Daly JM. Enhancement of interleukin-2 immunotherapy with L-arginine. Ann Surg 1992; 215:157-65; PMID:1546902; http://dx.doi.org/10.1097/00000658-199202000-00011
   PubMed Web of Science ®Google Scholar
• Hussain SF, Kong LY, Jordan J, Conrad C, Madden T, Fokt I, Priebe W, Heimberger AB. A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res 2007; 67:9630-6; PMID:17942891; http://dx.doi.org/10.1158/0008-5472.CAN-07-1243
   PubMed Web of Science ®Google Scholar
• Kong LY, Wu AS, Doucette T, Wei J, Priebe W, Fuller GN, Qiao W, Sawaya R, Rao G, Heimberger AB. Intratumoral mediated immunosuppression is prognostic in genetically engineered murine models of glioma and correlates to immunotherapeutic responses. Clin Cancer Res 2010; 16:5722-33; PMID:20921210; http://dx.doi.org/10.1158/1078-0432.CCR-10-1693
   PubMed Web of Science ®Google Scholar
• Wu A, Wei J, Kong LY, Wang Y, Priebe W, Qiao W, Sawaya R, Heimberger AB. Glioma cancer stem cells induce immunosuppressive macrophages/microglia. Neuro Oncol 2010; 12:1113-25; PMID:20667896; http://dx.doi.org/10.1093/neuonc/noq082
   PubMed Web of Science ®Google Scholar
• Oh T, Fakurnejad S, Sayegh ET, Clark AJ, Ivan ME, Sun MZ, Safaee M, Bloch O, James CD, Parsa AT. Immunocompetent murine models for the study of glioblastoma immunotherapy. J Transl Med 2014; 12:107; PMID:24779345; http://dx.doi.org/10.1186/1479-5876-12-107
   PubMed Web of Science ®Google Scholar
• Soliman H, Khalil F, Antonia S. PD-L1 expression is increased in a subset of basal type breast cancer cells. PLoS One 2014; 9:e88557; PMID:24551119; http://dx.doi.org/10.1371/journal.pone.0088557
   PubMed Web of Science ®Google Scholar
• Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014; 371:2189-99; PMID:25409260; http://dx.doi.org/10.1056/NEJMoa1406498
   PubMed Web of Science ®Google Scholar
• Champiat S, Ferte C, Lebel-Binay S, Eggermont A, Soria JC. Exomics and immunogenics: Bridging mutational load and immune checkpoints efficacy. Oncoimmunology 2014; 3:e27817; PMID:24605269; http://dx.doi.org/10.4161/onci.27817
   PubMed Web of Science ®Google Scholar
• Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, Sucker A, Hillen U, Geukes Foppen MH, Goldinger SM et al. Genomic correlates of response to CTLA4 blockade in metastatic melanoma. Science 2015; 9;350(6257):207–11; PMID:26359337; http://dx.doi.org/10.1126/science.aad0095.
   PubMed Web of Science ®Google Scholar
• Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17:2105-16; PMID:10561265
   PubMed Web of Science ®Google Scholar
• McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, Logan TF, Kirkwood JM, Gordon MS, Sosman JA, Ernstoff MS et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 2005; 23:133-41; PMID:15625368; http://dx.doi.org/10.1200/JCO.2005.03.206
   PubMed Web of Science ®Google Scholar
• Grauer OM, Molling JW, Bennink E, Toonen LW, Sutmuller RP, Nierkens S, Adema GJ. TLR ligands in the local treatment of established intracerebral murine gliomas. J Immunol 2008; 181:6720-9; PMID:18981089; http://dx.doi.org/10.4049/jimmunol.181.10.6720
   PubMed Web of Science ®Google Scholar
• Okada H, Butterfield LH, Hamilton RL, Hoji A, Sakaki M, Ahn BJ, Kohanbash G, Drappatz J, Engh J, Amankulor N et al. Induction of robust type-I CD8+ T-cell responses in WHO grade 2 low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC. Clin Cancer Res 2015; 21:286-94; PMID:25424847; http://dx.doi.org/10.1158/1078-0432.CCR-14-1790
   PubMed Web of Science ®Google Scholar
• Pollack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Potter DM, Connelly AK, Dibridge SA, Whiteside TL, Okada H. Antigen-specific immune responses and clinical outcome after vaccination with glioma-associated antigen peptides and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in children with newly diagnosed malignant brainstem and nonbrainstem gliomas. J Clin Oncol 2014; 32:2050-8; PMID:24888813; http://dx.doi.org/10.1200/JCO.2013.54.0526
   PubMed Web of Science ®Google Scholar
• Large-Scale Production of Monoclonal Antibodies. In: Antibodies. NRCUCoMoPM, ed. Monoclonal Antibody Production. Washington, DC: National Academies Press (US), 1999.
   Google Scholar
• Shaughnessy AF. Monoclonal antibodies: magic bullets with a hefty price tag. BMJ 2012; 345:e8346; PMID:23236036; http://dx.doi.org/10.1136/bmj.e8346
   PubMed Web of Science ®Google Scholar
• Frei K, Gramatzki D, Tritschler I, Schroeder JJ, Espinoza L, Rushing EJ, Weller M. Transforming growth factor-beta pathway activity in glioblastoma. Oncotarget 2015; 6:5963-77; PMID:25849941; http://dx.doi.org/10.18632/oncotarget.3467
   PubMed Web of Science ®Google Scholar
• Srivastava PK, Udono H, Blachere NE, Li Z. Heat shock proteins transfer peptides during antigen processing and CTL priming. [Review] [52 refs]. Immunogenetics 1994; 39:93-8; PMID:8276462; http://dx.doi.org/10.1007/BF00188611
   PubMed Web of Science ®Google Scholar
• Hu X, Miao W, Zou Y, Zhang W, Zhang Y, Liu H. Expression of p53, epidermal growth factor receptor, Ki-67 and O-methylguanine-DNA methyltransferase in human gliomas. Oncology letters 2013; 6:130-4; PMID:23946790; http://dx.doi.org/10.3892/ol.2013.1317
   PubMed Web of Science ®Google Scholar
• Nicholas MK, Lukas RV, Jafri NF, Faoro L, Salgia R. Epidermal growth factor receptor - mediated signal transduction in the development and therapy of gliomas. Clin Cancer Res 2006; 12:7261-70; PMID:17189397; http://dx.doi.org/10.1158/1078-0432.CCR-06-0874
   PubMed Web of Science ®Google Scholar
• Szulzewsky F, Pelz A, Feng X, Synowitz M, Markovic D, Langmann T, Holtman IR, Wang X, Eggen BJ, Boddeke HW et al. Glioma-associated microglia/macrophages display an expression profile different from m1 and m2 polarization and highly express gpnmb and spp1. PLoS One 2015; 10:e0116644; PMID:25658639; http://dx.doi.org/10.1371/journal.pone.0116644
   PubMed Web of Science ®Google Scholar
• Dziurzynski K, Chang SM, Heimberger AB, Kalejta RF, McGregor Dallas SR, Smit M, Soroceanu L, Cobbs CS. Consensus on the role of human cytomegalovirus in glioblastoma. Neuro Oncol 2012; 14:246-55; PMID:22319219; http://dx.doi.org/10.1093/neuonc/nor227
   PubMed Web of Science ®Google Scholar
• Debinski W, Gibo DM, Hulet SW, Connor JR, Gillespie GY. Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas. Clin Cancer Res 1999; 5:985-90; PMID:10353730
   PubMed Web of Science ®Google Scholar
• Debinski W, Gibo DM, Slagle B, Powers SK, Gillespie GY. Receptor for interleukin 13 is abundantly and specifically over-expressed in patients with glioblastoma multiforme. Int J Oncol 1999; 15:481-6; PMID:10427128; http://dx.doi.org/10.3892/ijo.15.3.481
   PubMed Web of Science ®Google Scholar
• Lacouture ME, Morris JC, Lawrence DP, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Berzofsky JA, Hsu FJ, Guitart J. Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor beta by the monoclonal antibody fresolimumab (GC1008). Cancer Immunol Immunother 2015; 64:437-46; PMID:25579378; http://dx.doi.org/10.1007/s00262-015-1653-0
   PubMed Web of Science ®Google Scholar
• Nemunaitis J, Dillman RO, Schwarzenberger PO, Senzer N, Cunningham C, Cutler J, Tong A, Kumar P, Pappen B, Hamilton C et al. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J Clin Oncol 2006; 24:4721-30; PMID:16966690; http://dx.doi.org/10.1200/JCO.2005.05.5335
   PubMed Web of Science ®Google Scholar
• Nemunaitis J, Nemunaitis M, Senzer N, Snitz P, Bedell C, Kumar P, Pappen B, Maples PB, Shawler D, Fakhrai H. Phase II trial of Belagenpumatucel-L, a TGF-beta2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients. Cancer Gene Ther 2009; 16:620-4; PMID:19287371; http://dx.doi.org/10.1038/cgt.2009.15
   PubMed Web of Science ®Google Scholar
• Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, Parmiani G, Tosti G, Kirkwood JM, Hoos A et al. Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group. J Clin Oncol 2008; 26:955-62; PMID:18281670; http://dx.doi.org/10.1200/JCO.2007.11.9941
   PubMed Web of Science ®Google Scholar
• Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363:411-22; PMID:20818862; http://dx.doi.org/10.1056/NEJMoa1001294
   PubMed Web of Science ®Google Scholar
• Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 2015; 372:311-9; PMID:25482239; http://dx.doi.org/10.1056/NEJMoa1411087
   PubMed Web of Science ®Google Scholar
• Brahmer JR, Hammers H, Lipson EJ. Nivolumab: targeting PD-1 to bolster antitumor immunity. Future Oncol 2015; 11:1307-26; PMID:25798726; http://dx.doi.org/10.2217/fon.15.52
   PubMed Web of Science ®Google Scholar
• Brayer J, Fishman M. Regression of metastatic clear cell kidney cancer with interleukin-2 treatment following nivolumab (anti-PD-1) treatment. J Immunother 2014; 37:187-91; PMID:24598453; http://dx.doi.org/10.1097/CJI.0000000000000024
   PubMed Web of Science ®Google Scholar
• Faghfuri E, Faramarzi MA, Nikfar S, Abdollahi M. Nivolumab and pembrolizumab as immune-modulating monoclonal antibodies targeting the PD-1 receptor to treat melanoma. Expert Rev Anticancer Ther 2015; 15:981-93; PMID:26313415; http://dx.doi.org/10.1586/14737140.2015.1074862
   PubMed Web of Science ®Google Scholar
• Geynisman DM. Anti-programmed Cell Death Protein 1 (PD-1) Antibody Nivolumab Leads to a Dramatic and Rapid Response in Papillary Renal Cell Carcinoma with Sarcomatoid and Rhabdoid Features. Eur Urol 2015; 68(5):912-4; PMID:26194044; http://dx.doi.org/10.1016/j.eururo.2015.07.008.
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366:2443-54; PMID:22658127; http://dx.doi.org/10.1056/NEJMoa1200690
   PubMed Web of Science ®Google Scholar
• Palucka AK, Dhodapkar MV, Paczesny S, Burkeholder S, Wittkowski KM, Steinman RM, Fay J, Banchereau J. Single injection of CD34+ progenitor-derived dendritic cell vaccine can lead to induction of T-cell immunity in patients with stage IV melanoma. J Immunother 2003; 26:432-9; PMID:12973032; http://dx.doi.org/10.1097/00002371-200309000-00006
   PubMed Web of Science ®Google Scholar
• Palucka AK, Dhodapkar MV, Paczesny S, Ueno H, Fay J, Banchereau J. Boosting vaccinations with peptide-pulsed CD34+ progenitor-derived dendritic cells can expand long-lived melanoma peptide-specific CD8+ T cells in patients with metastatic melanoma. J Immunother 2005; 28:158-68; PMID:15725960; http://dx.doi.org/10.1097/01.cji.0000154249.74383.17
   PubMed Web of Science ®Google Scholar
• Podrazil M, Horvath R, Becht E, Rozkova D, Bilkova P, Sochorova K, Hromadkova H, Kayserova J, Vavrova K, Lastovicka J et al. Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer. Oncotarget 2015; 6:18192-205; PMID:26078335; http://dx.doi.org/10.18632/oncotarget.4145
   PubMed Web of Science ®Google Scholar
• Kawakami K, Husain SR, Kawakami M, Puri RK. Improved anti-tumor activity and safety of interleukin-13 receptor targeted cytotoxin by systemic continuous administration in head and neck cancer xenograft model. Mol Med 2002; 8:487-94; PMID:12435859
   PubMed Web of Science ®Google Scholar
• Kawakami K, Kawakami M, Joshi BH, Puri RK. Interleukin-13 receptor-targeted cancer therapy in an immunodeficient animal model of human head and neck cancer. Cancer Res 2001; 61:6194-200; PMID:11507072
   PubMed Web of Science ®Google Scholar
• Kioi M, Kawakami M, Shimamura T, Husain SR, Puri RK. Interleukin-13 receptor alpha2 chain: a potential biomarker and molecular target for ovarian cancer therapy. Cancer 2006; 107:1407-18; PMID:16902988; http://dx.doi.org/10.1002/cncr.22134
   PubMed Web of Science ®Google Scholar
• Komohara Y, Horlad H, Ohnishi K, Ohta K, Makino K, Hondo H, Yamanaka R, Kajiwara K, Saito T, Kuratsu J et al. M2 macrophage/microglial cells induce activation of Stat3 in primary central nervous system lymphoma. Journal of clinical and experimental hematopathology: JCEH 2011; 51:93-9; PMID:22104307; http://dx.doi.org/10.3960/jslrt.51.93
   PubMedGoogle Scholar
• van den Bent MJ, Gao Y, Kerkhof M, Kros JM, Gorlia T, van Zwieten K, Prince J, van Duinen S, Sillevis Smitt PA, Taphoorn M et al. Changes in the EGFR amplification and EGFRvIII expression between paired primary and recurrent glioblastomas. Neuro Oncol 2015; 17:935-41; PMID:25691693; http://dx.doi.org/10.1093/neuonc/nov013
   PubMed Web of Science ®Google Scholar
• Lv S, Teugels E, Sadones J, De Brakeleer S, Duerinck J, Du Four S, Michotte A, De Greve J, Neyns B. Correlation of EGFR, IDH1 and PTEN status with the outcome of patients with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking monoclonal antibody cetuximab. Int J Oncol 2012; 41:1029-35; PMID:22752145; http://dx.doi.org/10.3892/ijo.2012.1539188
   PubMed Web of Science ®Google Scholar
• Martens T, Laabs Y, Gunther HS, Kemming D, Zhu Z, Witte L, Hagel C, Westphal M, Lamszus K. Inhibition of glioblastoma growth in a highly invasive nude mouse model can be achieved by targeting epidermal growth factor receptor but not vascular endothelial growth factor receptor-2. Clin Cancer Res 2008; 14:5447-58; PMID:18765536; http://dx.doi.org/10.1158/1078-0432.CCR-08-0147
   PubMed Web of Science ®Google Scholar
• Agarwalla P, Barnard Z, Fecci P, Dranoff G, Curry WT, Jr. Sequential immunotherapy by vaccination with GM-CSF-expressing glioma cells and CTLA-4 blockade effectively treats established murine intracranial tumors. J Immunother 2012; 35:385-9; PMID:22576343; http://dx.doi.org/10.1097/CJI.0b013e3182562d59
   PubMed Web of Science ®Google Scholar
• Peggs KS, Quezada SA, Chambers CA, Korman AJ, Allison JP. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med 2009; 206:1717-25; PMID:19581407; http://dx.doi.org/10.1084/jem.20082492
   PubMed Web of Science ®Google Scholar
• Quezada SA, Peggs KS, Curran MA, Allison JP. CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. Journal of Clinical Investigation 2006; 116:1935-45; PMID:16778987; http://dx.doi.org/10.1172/JCI27745
   PubMed Web of Science ®Google Scholar
• Kong S, Sengupta S, Tyler B, Bais AJ, Ma Q, Doucette S, Zhou J, Sahin A, Carter BS, Brem H et al. Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells. Clin Cancer Res 2012; 18:5949-60; PMID:22966020; http://dx.doi.org/10.1158/1078-0432.CCR-12-0319
   PubMed Web of Science ®Google Scholar
• Scott AM, Lee FT, Tebbutt N, Herbertson R, Gill SS, Liu Z, Skrinos E, Murone C, Saunder TH, Chappell B et al. A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors. Proc Natl Acad Sci U S A 2007; 104:4071-6; PMID:17360479; http://dx.doi.org/10.1073/pnas.0611693104
   PubMed Web of Science ®Google Scholar
• Coniglio SJ, Eugenin E, Dobrenis K, Stanley ER, West BL, Symons MH, Segall JE. Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol Med 2012; 18:519-27; PMID:22294205; http://dx.doi.org/10.2119/molmed.2011.00217
   PubMed Web of Science ®Google Scholar
• Markovic DS, Vinnakota K, Chirasani S, Synowitz M, Raguet H, Stock K, Sliwa M, Lehmann S, Kalin R, van Rooijen N et al. Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci U S A 2009; 106:12530-5; PMID:19617536; http://dx.doi.org/10.1073/pnas.0804273106
   PubMed Web of Science ®Google Scholar
• Kim JE, Patel MA, Mangraviti A, Velarde E, Theodros D, Mathios D, Jackson CM, Tyler B, Ye X, Brem H et al. 143 The Combination of anti-TIM-3 and anti-PD-1 Checkpoint Inhibitors With Focused Radiation Resulted in a Synergistic Antitumor Immune Response in a Preclinical Glioma Model. Neurosurgery 2015; 62 Suppl 1):212; http://dx.doi.org/10.1227/01.neu.0000467105.60300.04
   Google Scholar
• Penuelas S, Anido J, Prieto-Sanchez RM, Folch G, Barba I, Cuartas I, Garcia-Dorado D, Poca MA, Sahuquillo J, Baselga J et al. TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma. Cancer Cell 2009; 15:315-27; PMID:19345330; http://dx.doi.org/10.1016/j.ccr.2009.02.011
   PubMed Web of Science ®Google Scholar
• Hardee ME, Marciscano AE, Medina-Ramirez CM, Zagzag D, Narayana A, Lonning SM, Barcellos-Hoff MH. Resistance of glioblastoma-initiating cells to radiation mediated by the tumor microenvironment can be abolished by inhibiting transforming growth factor-beta. Cancer Res 2012; 72:4119-29; PMID:22693253; http://dx.doi.org/10.1158/0008-5472.CAN-12-0546
   PubMed Web of Science ®Google Scholar
• Randriarimanana T, Chateau A, Faivre B, Pinel S, Boura C. Sensitivity of glioma initiating cells to a monoclonal anti-EGFR antibody therapy under hypoxia. Life Sci 2015; 137:74-80; PMID:26239438; http://dx.doi.org/10.1016/j.lfs.2015.07.024
   PubMed Web of Science ®Google Scholar
• Xu Q, Liu G, Yuan X, Xu M, Wang H, Ji J, Konda B, Black KL, Yu JS. Antigen-specific T-cell response from dendritic cell vaccination using cancer stem-like cell-associated antigens. Stem Cells 2009; 27:1734-40; PMID:19536809; http://dx.doi.org/10.1002/stem.102
   PubMed Web of Science ®Google Scholar
• Pellegatta S, Poliani PL, Corno D, Menghi F, Ghielmetti F, Suarez-Merino B, Caldera V, Nava S, Ravanini M, Facchetti F et al. Neurospheres enriched in cancer stem-like cells are highly effective in eliciting a dendritic cell-mediated immune response against malignant gliomas. Cancer Res 2006; 66:10247-52; PMID:17079441; http://dx.doi.org/10.1158/0008-5472.CAN-06-2048
   PubMed Web of Science ®Google Scholar
• Vik-Mo EO, Nyakas M, Mikkelsen BV, Moe MC, Due-Tonnesen P, Suso EM, Saeboe-Larssen S, Sandberg C, Brinchmann JE, Helseth E et al. Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunol Immunother 2013; 62:1499-509; PMID:23817721; http://dx.doi.org/10.1007/s00262-013-1453-3
   PubMed Web of Science ®Google Scholar
• Zhu X, Prasad S, Gaedicke S, Hettich M, Firat E, Niedermann G. Patient-derived glioblastoma stem cells are killed by CD133-specific CAR T cells but induce the T cell aging marker CD57. Oncotarget 2015; 6:171-84; PMID:25426558; http://dx.doi.org/10.18632/oncotarget.2767
   PubMed Web of Science ®Google Scholar
• Wei Q, Clarke L, Scheidenhelm DK, Qian B, Tong A, Sabha N, Karim Z, Bock NA, Reti R, Swoboda R et al. High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model. Cancer Res 2006; 66:7429-37; PMID:16885338; http://dx.doi.org/10.1158/0008-5472.CAN-06-0712
   PubMed Web of Science ®Google Scholar
• Holland EC, Hively WP, DePinho RA, Varmus HE. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice. Genes Dev 1998; 12:3675-85; PMID:9851974; http://dx.doi.org/10.1101/gad.12.23.3675
   PubMed Web of Science ®Google Scholar
• Belcaid Z, Phallen JA, Zeng J, See AP, Mathios D, Gottschalk C, Nicholas S, Kellett M, Ruzevick J, Jackson C et al. Focal radiation therapy combined with 4-1BB activation and CTLA-4 blockade yields long-term survival and a protective antigen-specific memory response in a murine glioma model. PLoS One 2014; 9:e101764; PMID:25013914; http://dx.doi.org/10.1371/journal.pone.0101764
   PubMed Web of Science ®Google Scholar
• Vom Berg J, Vrohlings M, Haller S, Haimovici A, Kulig P, Sledzinska A, Weller M, Becher B. Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell-mediated glioma rejection. J Exp Med 2013; 210:2803-11; PMID:24277150; http://dx.doi.org/10.1084/jem.20130678
   PubMed Web of Science ®Google Scholar
• Fecci PE, Sweeney AE, Grossi PM, Nair SK, Learn CA, Mitchell DA, Cui X, Cummings TJ, Bigner DD, Gilboa E et al. Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells. Clin Cancer Res 2006; 12:4294-305; PMID:16857805; http://dx.doi.org/10.1158/1078-0432.CCR-06-0053
   PubMed Web of Science ®Google Scholar
• Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA. In vitro killing of human glioblastoma by interleukin-2- activated autologous lymphocytes. JNeurosurg 1986; 64:114-7; PMID:3001247; http://dx.doi.org/10.3171/jns.1986.64.1.0114
   Web of Science ®Google Scholar
• Jacobs SK, Melin G, Holcomb B, Parham CW, Kornblith PL, Grimm EA. Lymphokine activated killer (LAK) cell-mediated lysis of murine glioma: trypsin-chymotrypsin-sensitive glioma protein is responsible for tumor-selective recognition by LAK cells. Brain Res 1986; 372:386-9; PMID:3486696; http://dx.doi.org/10.1016/0006-8993(86)91150-9
   PubMed Web of Science ®Google Scholar
• Jacobs SK, Parham CW, Holcomb B, Ikejiri B, Kornblith PL, Grimm EA. Lymphokine activated killer (LAK) cell mediated killing of human glioma: effect of pretreating glioma with various membrane modifying agents. J Neurooncol 1987; 5:5-10; PMID:3037036; http://dx.doi.org/10.1007/BF00162760
   PubMed Web of Science ®Google Scholar
• Wang P, Yu JP, Gao SY, An XM, Ren XB, Wang XG, Li WL. Experimental study on the treatment of intracerebral glioma xenograft with human cytokine-induced killer cells. Cell Immunol 2008; 253:59-65; PMID:18522858; http://dx.doi.org/10.1016/j.cellimm.2008.04.014
   PubMed Web of Science ®Google Scholar
• Poli A, Wang J, Domingues O, Planaguma J, Yan T, Rygh CB, Skaftnesmo KO, Thorsen F, McCormack E, Hentges F et al. Targeting glioblastoma with NK cells and mAb against NG2/CSPG4 prolongs animal survival. Oncotarget 2013; 4:1527-46; PMID:24127551; http://dx.doi.org/10.18632/oncotarget.1291
   PubMed Web of Science ®Google Scholar
• Barrett JA, Hongliang C, Miao J, Murray M, Gable E, Blake D, Krishnan S, Chiocca EA, Nagpal S, Raizer J, et al. Intratumoral regulated expression of IL-12 as a gene therapy approach to treatment of glioma. Neuro Oncol 2015; 17(suppl 5):v113–v115; doi: http://dx.doi.org/10.1093/neuonc/nov217.03.
   Google Scholar
• Sampson JH, Archer GE, Mitchell DA, Heimberger AB, Herndon JE, 2nd, Lally-Goss D, McGehee-Norman S, Paolino A, Reardon DA, Friedman AH et al. An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol Cancer Ther 2009; 8:2773-9; PMID:19825799; http://dx.doi.org/10.1158/1535-7163.MCT-09-0124
   PubMed Web of Science ®Google Scholar
• Schlingensiepen R, Goldbrunner M, Szyrach MN, Stauder G, Jachimczak P, Bogdahn U, Schulmeyer F, Hau P, Schlingensiepen KH. Intracerebral and intrathecal infusion of the TGF-beta 2-specific antisense phosphorothioate oligonucleotide AP 12009 in rabbits and primates: toxicology and safety. Oligonucleotides 2005; 15:94-104; PMID:15989424; http://dx.doi.org/10.1089/oli.2005.15.94
   PubMed Web of Science ®Google Scholar
• Hasselbalch B, Lassen U, Hansen S, Holmberg M, Sorensen M, Kosteljanetz M, Broholm H, Stockhausen MT, Poulsen HS. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial. Neuro Oncol 2010; 12:508-16; PMID:20406901; http://dx.doi.org/10.1093/neuonc/nop063
   PubMed Web of Science ®Google Scholar
• Ansell SM, Hurvitz SA, Koenig PA, LaPlant BR, Kabat BF, Fernando D, Habermann TM, Inwards DJ, Verma M, Yamada R et al. Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res 2009; 15:6446-53; PMID:19808874; http://dx.doi.org/10.1158/1078-0432.CCR-09-1339
   PubMed Web of Science ®Google Scholar
• Horinouchi H, Yamamoto N, Fujiwara Y, Sekine I, Nokihara H, Kubota K, Kanda S, Yagishita S, Wakui H, Kitazono S et al. Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer. Invest New Drugs 2015; 33:881-9; PMID:25924991; http://dx.doi.org/10.1007/s10637-015-0243-5
   PubMed Web of Science ®Google Scholar
• McDermott D, Haanen J, Chen TT, Lorigan P, O'Day S, Investigators MDX. Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20). Ann Oncol 2013; 24:2694-8; PMID:23942774; http://dx.doi.org/10.1093/annonc/mdt291
   PubMed Web of Science ®Google Scholar
• O'Day SJ, Maio M, Chiarion-Sileni V, Gajewski TF, Pehamberger H, Bondarenko IN, Queirolo P, Lundgren L, Mikhailov S, Roman L et al. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Ann Oncol 2010; 21:1712-7; PMID:20147741; http://dx.doi.org/10.1093/annonc/mdq013
   PubMed Web of Science ®Google Scholar
• Weber J, Hamid O, Amin A, O'Day S, Masson E, Goldberg SM, Williams D, Parker SM, Chasalow SD, Alaparthy S et al. Randomized phase I pharmacokinetic study of ipilimumab with or without one of two different chemotherapy regimens in patients with untreated advanced melanoma. Cancer Immun 2013; 13:7; PMID:23833564
   PubMedGoogle Scholar
• Weber JS, Amin A, Minor D, Siegel J, Berman D, O'Day SJ. Safety and clinical activity of ipilimumab in melanoma patients with brain metastases: retrospective analysis of data from a phase 2 trial. Melanoma Res 2011; 21:530-4; PMID:22051508; http://dx.doi.org/10.1097/CMR.0b013e32834d3d88
   PubMed Web of Science ®Google Scholar
• Weber JS, O'Day S, Urba W, Powderly J, Nichol G, Yellin M, Snively J, Hersh E. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol 2008; 26:5950-6; PMID:19018089; http://dx.doi.org/10.1200/JCO.2008.16.1927
   PubMed Web of Science ®Google Scholar
• Chang CN, Huang YC, Yang DM, Kikuta K, Wei KJ, Kubota T, Yang WK. A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma. J Clin Neurosci 2011; 18:1048-54; PMID:21715171; http://dx.doi.org/10.1016/j.jocn.2010.11.034
   PubMed Web of Science ®Google Scholar
• Iwami K, Shimato S, Ohno M, Okada H, Nakahara N, Sato Y, Yoshida J, Suzuki S, Nishikawa H, Shiku H et al. Peptide-pulsed dendritic cell vaccination targeting interleukin-13 receptor alpha2 chain in recurrent malignant glioma patients with HLA-A*24/A*02 allele. Cytotherapy 2012; 14:733-42; PMID:22424217; http://dx.doi.org/10.3109/14653249.2012.666633
   PubMed Web of Science ®Google Scholar
• Phuphanich S, Wheeler CJ, Rudnick JD, Mazer M, Wang H, Nuno MA, Richardson JE, Fan X, Ji J, Chu RM et al. Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother 2013; 62:125-35; PMID:22847020; http://dx.doi.org/10.1007/s00262-012-1319-0
   PubMed Web of Science ®Google Scholar
• Trepiakas R, Berntsen A, Hadrup SR, Bjorn J, Geertsen PF, Straten PT, Andersen MH, Pedersen AE, Soleimani A, Lorentzen T et al. Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial. Cytotherapy 2010; 12:721-34; PMID:20429791; http://dx.doi.org/10.3109/14653241003774045
   PubMed Web of Science ®Google Scholar
• Yamanaka R, Abe T, Yajima N, Tsuchiya N, Homma J, Kobayashi T, Narita M, Takahashi M, Tanaka R. Vaccination of recurrent glioma patients with tumor lysate-pulsed dendritic cells elicits immune responses: Results of a clinical phase I/II trial. Br J Cancer 2003; 89:1172-9; PMID:14520441; http://dx.doi.org/10.1038/sj.bjc.6601268
   PubMed Web of Science ®Google Scholar
• Nemunaitis JJ, Linette GP, Hamid O, Agarwala SS, Starodub A, Sun L, Lebel F, Barrett JA, Lewis J. Regulated intratumoral expression of IL-12 as a basis for combination therapy in melanoma. J Transl Med. 2014; 12(Suppl 1):O11; http:dx.doi.org/10.1186/1479-5876-12-S1-O11.
   Google Scholar
• Sampson JH, Archer GE, Mitchell DA, Heimberger AB, Bigner DD. Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma. Semin Immunol 2008; 20:267-75; PMID:18539480; http://dx.doi.org/10.1016/j.smim.2008.04.001
   PubMed Web of Science ®Google Scholar
• Lebbe C, Weber JS, Maio M, Neyns B, Harmankaya K, Hamid O, O'Day SJ, Konto C, Cykowski L, McHenry MB et al. Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies. Ann Oncol 2014; 25:2277-84; PMID:25210016; http://dx.doi.org/10.1093/annonc/mdu441
   PubMed Web of Science ®Google Scholar
• Neyns B, Sadones J, Joosens E, Bouttens F, Verbeke L, Baurain JF, D'Hondt L, Strauven T, Chaskis C, In't Veld P et al. Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol 2009; 20:1596-603; PMID:19491283; http://dx.doi.org/10.1093/annonc/mdp032
   PubMed Web of Science ®Google Scholar
• Fakhrai H, Mantil JC, Liu L, Nicholson GL, Murphy-Satter CS, Ruppert J, Shawler DL. Phase I clinical trial of a TGF-beta antisense-modified tumor cell vaccine in patients with advanced glioma. Cancer Gene Ther 2006; 13:1052-60; PMID:16826191; http://dx.doi.org/10.1038/sj.cgt.7700975
   PubMed Web of Science ®Google Scholar
• Mitsuka K, Kawataki T, Satoh E, Asahara T, Horikoshi T, Kinouchi H. Expression of indoleamine 2,3-dioxygenase and correlation with pathological malignancy in gliomas. Neurosurgery 2013; 72:1031-8; discussion 8-9; PMID:23426156; http://dx.doi.org/10.1227/NEU.0b013e31828cf945
   PubMed Web of Science ®Google Scholar
• Wainwright DA, Balyasnikova IV, Chang AL, Ahmed AU, Moon KS, Auffinger B, Tobias AL, Han Y, Lesniak MS. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clin Cancer Res 2012; 18:6110-21; PMID:22932670; http://dx.doi.org/10.1158/1078-0432.CCR-12-2130
   PubMed Web of Science ®Google Scholar
• Horiguchi A, Oya M, Marumo K, Murai M. STAT3, but not ERKs, mediates the IL-6-induced proliferation of renal cancer cells, ACHN and 769P. Kidney international 2002; 61:926-38; PMID:11849447; http://dx.doi.org/10.1046/j.1523-1755.2002.00206.x
   PubMed Web of Science ®Google Scholar
• Khoury JD, Medeiros LJ, Rassidakis G, Yared MA, Tsioli P, Leventaki V, Schmitt-Graeff A, Herling M, Amin HM, Lai R. Differential expression and clinical significance of tyrosine-phosphorylated STAT3 in ALK+ and ALK- anaplastic large cell lymphoma. Clin Cancer Res 2003; 9:3692-9; PMID:14506160
   PubMed Web of Science ®Google Scholar
• Masuda M, Toh S, Koike K, Kuratomi Y, Suzui M, Deguchi A, Komiyama S, Weinstein IB. The roles of JNK1 and Stat3 in the response of head and neck cancer cell lines to combined treatment with all-trans-retinoic acid and 5-fluorouracil. Jpn J Cancer Res 2002; 93:329-39; PMID:11927016; http://dx.doi.org/10.1111/j.1349-7006.2002.tb02176.x
   PubMedGoogle Scholar
• McLoughlin RM, Jenkins BJ, Grail D, Williams A, Fielding C, Parker CR, Ernst M, Topley N, Jones SA. IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation. Proc Natl Acad Sci U S A 2005 102:9589-94; PMID:15976028; http://dx.doi.org/10.1073/pnas.0501794102
   PubMed Web of Science ®Google Scholar
• Gong W, Wang L, Yao J, Ajani JA, Wei D, Aldape K, Xie K, Sawaya R, Huang S. Expression of activated signal transducer and activator of transcription 3 predicts expression of vascular endothelial growth factor in and angiogenic phenotype of human gastric cancer. Clin Cancer Res 2005; 11:1386-93; PMID:15746037; http://dx.doi.org/10.1158/1078-0432.CCR-04-0487
   PubMed Web of Science ®Google Scholar
• Horiguchi A, Oya M, Shimada T, Uchida A, Marumo K, Murai M. Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: A study of incidence and its association with pathological features and clinical outcome. J Urology 2002; 168:762-5; PMID:12131365; http://dx.doi.org/10.1016/S0022-5347(05)64741-6
   PubMed Web of Science ®Google Scholar
• Masuda M, Suzui M, Yasumatu R. Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res 2002; 62:3351-5; PMID:12067972
   PubMed Web of Science ®Google Scholar
• Kupferman ME, Jayakumar A, Zhou G, Xie T, Dakak-Yazici Y, Zhao M, Ju J, Mandal M, Jasser S, Madden T et al. Therapeutic suppression of constitutive and inducible JAK\STAT activation in head and neck squamous cell carcinoma. J Exp Ther Oncol 2009; 8:117-27; PMID:20192118
   PubMedGoogle Scholar
• Xi S, Gooding WE, Grandis JR. In vivo antitumor efficacy of STAT3 blockade using a transcription factor decoy approach: implications for cancer therapy. Oncogene 2005; 24:970-9; PMID:15592503; http://dx.doi.org/10.1038/sj.onc.1208316
   PubMed Web of Science ®Google Scholar
• de Groot J, Liang J, Kong LY, Wei J, Piao Y, Fuller G, Qiao W, Heimberger AB. Modulating antiangiogenic resistance by inhibiting the signal transducer and activator of transcription 3 pathway in glioblastoma. Oncotarget 2012; 3:1036-48; PMID:23013619; http://dx.doi.org/10.18632/oncotarget.663
   PubMed Web of Science ®Google Scholar
• Bleeker FE, Lamba S, Leenstra S, Troost D, Hulsebos T, Vandertop WP, Frattini M, Molinari F, Knowles M, Cerrato A et al. IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 2009; 30:7-11; PMID:19117336; http://dx.doi.org/10.1002/humu.20937
   PubMed Web of Science ®Google Scholar
• Kong LY, Abou-Ghazal MK, Wei J, Chakraborty A, Sun W, Qiao W, Fuller GN, Fokt I, Grimm EA, Schmittling RJ et al. A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells. Clin Cancer Res 2008; 14:5759-68; PMID:18794085; http://dx.doi.org/10.1158/1078-0432.CCR-08-0377
   PubMed Web of Science ®Google Scholar
• Choi BD, Kuan CT, Cai M, Archer GE, Mitchell DA, Gedeon PC, Sanchez-Perez L, Pastan I, Bigner DD, Sampson JH. Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma. Proc Natl Acad Sci U S A 2013; 110:270-5; PMID:23248284; http://dx.doi.org/10.1073/pnas.1219817110
   PubMed Web of Science ®Google Scholar
• Sampson JH, Choi BD, Sanchez-Perez L, Suryadevara CM, Snyder DJ, Flores CT, Schmittling RJ, Nair SK, Reap EA, Norberg PK et al. EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss. Clin Cancer Res 2014; 20:972-84; PMID:24352643; http://dx.doi.org/10.1158/1078-0432.CCR-13-0709
   PubMed Web of Science ®Google Scholar
• Caruso HG, Hurton LV, Najjar A, Rushworth D, Ang S, Olivares S, Mi T, Switzer K, Singh H, Huls H et al. Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity. Cancer Res 2015; 75:3505-18; PMID:26330164; http://dx.doi.org/10.1158/0008-5472.CAN-15-0139
   PubMed Web of Science ®Google Scholar
• Schumacher T, Bunse L, Pusch S, Sahm F, Wiestler B, Quandt J, Menn O, Osswald M, Oezen I, Ott M et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 2014; 512(7514):324-7; PMID:25043048; http://dx.doi.org/10.1038/nature13387.
   PubMed Web of Science ®Google Scholar
• Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellstrom KE, Mittler RS, Chen L. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med 1997; 3:682-5; PMID:9176498; http://dx.doi.org/10.1038/nm0697-682
   PubMed Web of Science ®Google Scholar
• Pollok KE, Kim YJ, Zhou Z, Hurtado J, Kim KK, Pickard RT, Kwon BS. Inducible T cell antigen 4-1BB. Analysis of expression and function. J Immunol 1993; 150:771-81; PMID:7678621
   PubMed Web of Science ®Google Scholar
• Shuford WW, Klussman K, Tritchler DD, Loo DT, Chalupny J, Siadak AW, Brown TJ, Emswiler J, Raecho H, Larsen CP et al. 4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J Exp Med 1997; 186:47-55; PMID:9206996; http://dx.doi.org/10.1084/jem.186.1.47
   PubMed Web of Science ®Google Scholar
• Kong G, Anyarambhatla G, Petros WP, Braun RD, Colvin OM, Needham D, Dewhirst MW. Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res 2000; 60:6950-7; PMID:11156395
   PubMed Web of Science ®Google Scholar
• Han J, Chu J, Keung Chan W, Zhang J, Wang Y, Cohen JB, Victor A, Meisen WH, Kim SH, Grandi P et al. CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells. Sci Rep 2015; 5:11483; PMID:26155832; http://dx.doi.org/10.1038/srep11483
   PubMed Web of Science ®Google Scholar
• Schrand B, Berezhnoy A, Brenneman R, Williams A, Levay A, Kong LY, Rao G, Zhou S, Heimberger AB, Gilboa E. Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer conjugates enhances the therapeutic index of tumor immunotherapy. Cancer Immunol Res 2014; 2:867-77; PMID:24938283; http://dx.doi.org/10.1158/2326-6066.CIR-14-0007
   PubMed Web of Science ®Google Scholar
• Iwamaru A, Szymanski S, Iwado E, Aoki H, Yokoyama T, Fokt I, Hess K, Conrad C, Madden T, Sawaya R et al. A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo. Oncogene 2007; 26:2435-44; PMID:17043651; http://dx.doi.org/10.1038/sj.onc.1210031
   PubMed Web of Science ®Google Scholar
• Kocak E, Lute K, Chang X, May KF, Jr., Exten KR, Zhang H, Abdessalam SF, Lehman AM, Jarjoura D, Zheng P et al. Combination therapy with anti-CTL antigen-4 and anti-4-1BB antibodies enhances cancer immunity and reduces autoimmunity. Cancer Res 2006; 66:7276-84; PMID:16849577; http://dx.doi.org/10.1158/0008-5472.CAN-05-2128
   PubMed Web of Science ®Google Scholar
• Schrand B, Berezhnoy A, Brenneman R, Williams A, Levay A, Gilboa E. Reducing toxicity of 4-1BB costimulation: targeting 4-1BB ligands to the tumor stroma with bi-specific aptamer conjugates. Oncoimmunology 2015; 4:e970918; PMID:25949891; http://dx.doi.org/10.4161/21624011.2014.970918
   PubMed Web of Science ®Google Scholar
• Daly JM, Reynolds J, Thom A, Kinsley L, Dietrick-Gallagher M, Shou J, Ruggieri B. Immune and metabolic effects of arginine in the surgical patient. Ann Surg 1988; 208:512-23; PMID:3140744; http://dx.doi.org/10.1097/00000658-198810000-00013
   PubMed Web of Science ®Google Scholar