Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines

References

• Malek TR, Yu A, Zhu L, Matsutani T, Adeegbe D, Bayer A. L. IL-2 family of cytokines in T regulatory cell development and homeostasis. J Clin Immunol 2008; 28:635-9; PMID:18726679; http://dx.doi.org/10.1007/s10875-008-9235-y
   PubMed Web of Science ®Google Scholar
• Kasprzak A, Olejniczak K, Przybyszewska W, Zabel M. Cellular expression of interleukin 2 (IL-2) and its receptor (IL-2R, CD25) in lung tumours. Folia Morphol (Warsz) 2007; 66:159-66; PMID:17985312
   PubMedGoogle Scholar
• Waldmann TA. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol 2006; 6:595-601; PMID:16868550; http://dx.doi.org/10.1038/nri1901
   PubMed Web of Science ®Google Scholar
• Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 2012; 12:180-90; PMID:22343569; http://dx.doi.org/10.1038/nri3156
   PubMed Web of Science ®Google Scholar
• Arenas-Ramirez N, Woytschak J, Boyman O. Interleukin-2: Biology, Design and Application. Trends Immunol 2015; 36:763-77; PMID:26572555; http://dx.doi.org/10.1016/j.it.2015.10.003
   PubMed Web of Science ®Google Scholar
• Boyman O, Krieg C, Homann D, Sprent J. Homeostatic maintenance of T cells and natural killer cells. Cell Mol Life Sci 2012; 69:1597-608; PMID:22460580; http://dx.doi.org/10.1007/s00018-012-0968-7
   PubMed Web of Science ®Google Scholar
• Fontenot JD, Rasmussen JP, Gavin MA, Rudensky A. Y. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 2005; 6:1142-51; PMID:16227984; http://dx.doi.org/10.1038/ni1263
   PubMed Web of Science ®Google Scholar
• D'Cruz LM, Klein L. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol 2005; 6:1152-59; PMID:16227983; http://dx.doi.org/10.1038/ni1264
   PubMed Web of Science ®Google Scholar
• Maloy KJ, Powrie F. Fueling regulation: IL-2 keeps CD4+ Treg cells fit. Nat Immunol 2005; 6:1071-72; PMID:16239920; http://dx.doi.org/10.1038/ni1105-1071
   PubMed Web of Science ®Google Scholar
• Rosenberg SA IL-2: the first effective immunotherapy for human cancer. J Immunol 2014; 192:5451-58; PMID:24907378; http://dx.doi.org/10.4049/jimmunol.1490019
   PubMed Web of Science ®Google Scholar
• Krieg C, Letourneau S, Pantaleo G, Boyman O. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci U S A 2010; 107:11906-11; PMID:20547866; http://dx.doi.org/10.1073/pnas.1002569107
   PubMed Web of Science ®Google Scholar
• Kontermann RE. Antibody-cytokine fusion proteins. Arch Biochem Biophys 2012; 526:194-205; PMID:22445675; http://dx.doi.org/10.1016/j.abb.2012.03.001
   PubMed Web of Science ®Google Scholar
• Pasche N, Neri D. Immunocytokines: a novel class of potent armed antibodies. Drug Discov Today 2012; 17:583-90; PMID:22289353; http://dx.doi.org/10.1016/j.drudis.2012.01.007
   PubMed Web of Science ®Google Scholar
• Ortiz-Sanchez E, Helguera G, Daniels TR, Penichet ML. Antibody-cytokine fusion proteins: applications in cancer therapy. Expert Opin Biol Ther 2008; 8:609632; PMID:18407765; http://dx.doi.org/10.1517/14712598.8.5.609
   PubMed Web of Science ®Google Scholar
• Lode HN, Xiang R, Perri P, Pertl U, Lode A, Gillies SD, Reisfeld RA. What to do with targeted IL-2. Drugs Today (Barc) 2000; 36:321-36; PMID:12861355; http://dx.doi.org/10.1358/dot.2000.36.5.575044
   PubMed Web of Science ®Google Scholar
• Lode HN, Xiang R, Becker JC, Gillies SD, Reisfeld R A. Immunocytokines: a promising approach to cancer immunotherapy. Pharmacol Ther 1998; 80:277-92; PMID:9888698; http://dx.doi.org/10.1016/S0163-7258(98)00033-3
   PubMed Web of Science ®Google Scholar
• Tzeng A, Kwan BH, Opel CF, Navaratna T, Wittrup KD. Antigen specificity can be irrelevant to immunocytokine efficacy and biodistribution. Proc Natl Acad Sci U S A 2015; 112:3320-3325; PMID:25733854; http://dx.doi.org/10.1073/pnas.1416159112
   PubMed Web of Science ®Google Scholar
• Zhu EF, Gai SA, Opel CF, Kwan BH, Surana R, Mihm MC, Kauke MJ, Moynihan KD, Angelini A, Williams RT et al. Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2. Cancer Cell 2015; 27:489-501; PMID:25873172; http://dx.doi.org/10.1016/j.ccell.2015.03.004
   PubMed Web of Science ®Google Scholar
• Moynihan KD, Opel CF, Szeto GL, Tzeng A, Zhu E F, Engreitz JM, Williams RT, Rakhra K, Zhang MH, Rothschilds AM et al. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat Med 2016; 22(12):1402-10; PMID:27775706; http://dx.doi.org/10.1038/nm.4200
   PubMed Web of Science ®Google Scholar
• Ashraf SQ, Umana P, Mossner E, Ntouroupi T, Brunker P, Schmidt C, Wilding JL, Mortensen NJ, Bodmer WF. Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis. Br J Cancer 2009; 101:1758-68; PMID:19904275; http://dx.doi.org/10.1038/sj.bjc.6605355
   PubMed Web of Science ®Google Scholar
• Durbin H, Young S, Stewart LM, Wrba F, Rowan A J, Snary D, Bodmer WF. An epitope on carcinoembryonic antigen defined by the clinically relevant antibody PR1A3. Proc Natl Acad Sci U S A 1994; 91:4313-17; PMID:7514303; http://dx.doi.org/10.1073/pnas.91.10.4313
   PubMed Web of Science ®Google Scholar
• Wilkinson RW, Ross EL, Poulsom R, Ilyas M, Straub J, Snary D, Bodmer WF, Mather SJ. Antibody targeting studies in a transgenic murine model of spontaneous colorectal tumors. Proc Natl Acad Sci U S A 2001; 98:10256-260; PMID:11517330; http://dx.doi.org/10.1073/pnas.181353498
   PubMed Web of Science ®Google Scholar
• Bacac M, Klein C, Umana P. CEA TCB: A novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors. Oncoimmunology 2016; 5:e1203498; PMID:27622073; http://dx.doi.org/10.1080/2162402X.2016.1203498
   PubMed Web of Science ®Google Scholar
• Lehmann S, Perera R, Grimm HP, Sam J, Colombetti S, Fauti T, Fahrni L, Schaller T, Freimoser-Grundschober A, Zielonka J et al. In Vivo Fluorescence Imaging of the Activity of CEA TCB, a Novel T-Cell Bispecific Antibody, Reveals Highly Specific Tumor Targeting and Fast Induction of T-Cell-Mediated Tumor Killing. Clin Cancer Res 2016; 22:4417-27; PMID:27117182; http://dx.doi.org/10.1158/1078-0432.CCR-15-2622
   PubMed Web of Science ®Google Scholar
• Bacac M, Fauti T, Sam J, Colombetti S, Weinzierl T, Ouaret D, Bodmer W, Lehmann S, Hofer T, Hosse RJ et al. A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors. Clin Cancer Res 2016; 22:3286-97; PMID:26861458; http://dx.doi.org/10.1158/1078-0432.CCR-15-1696
   PubMed Web of Science ®Google Scholar
• Goldstein MJ, Mitchell EP. Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer Invest 2005; 23:338-51; PMID:16100946; http://dx.doi.org/10.1081/CNV-58878
   PubMed Web of Science ®Google Scholar
• Oberst MD, Fuhrmann S, Mulgrew K, Amann M, Cheng L, Lutterbuese P, Richman L, Coats S, Baeuerle PA, Hammond SA. CEA/CD3 bispecific antibody MEDI-565/AMG 211 activation of T cells and subsequent killing of human tumors is independent of mutations commonly found in colorectal adenocarcinomas. MAbs 2014; 6:1571-84; PMID:25484061; http://dx.doi.org/10.4161/19420862.2014.975660
   PubMed Web of Science ®Google Scholar
• Peng L, Oberst MD, Huang J, Brohawn P, Morehouse C, Lekstrom K, Baeuerle PA, Wu H, Yao Y, Coats SR et al. The CEA/CD3-bispecific antibody MEDI-565 (MT111) binds a nonlinear epitope in the full-length but not a short splice variant of CEA. PLoS One 2012; 7:e36412; PMID:22574157; http://dx.doi.org/10.1371/journal.pone.0036412
   PubMed Web of Science ®Google Scholar
• Bacac M, Fauti T, Sam J, Colombetti S, Weinzierl T, Ouaret D, Bodmer WF, Lehmann S, Hofer T, Hosse RJ et al. A Novel Carcinoembryonic Antigen T Cell Bispecific Antibody (Cea Tcb) for the Treatment of Solid Tumors. Clin Cancer Res 2016; 22(13):3286-97; PMID:26861458; http://dx.doi.org/10.1158/1078-0432.CCR-15-1696
   PubMed Web of Science ®Google Scholar
• Govindan SV, Cardillo TM, Rossi EA, Trisal P, McBride WJ, Sharkey RM, Goldenberg DM. Improving the therapeutic index in cancer therapy by using antibody-drug conjugates designed with a moderately cytotoxic drug. Mol Pharm 2015; 12:1836-47; PMID:25402018; http://dx.doi.org/10.1021/mp5006195
   PubMed Web of Science ®Google Scholar
• Dabbs DJ, Sturtz K, Zaino RJ. The immunohistochemical discrimination of endometrioid adenocarcinomas. Hum Pathol 1996; 27:172-7; PMID:8617459; http://dx.doi.org/10.1016/S0046-8177(96)90371-8
   PubMed Web of Science ®Google Scholar
• Thompson JA, Grunert F, Zimmermann W. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J Clin Lab Anal 1991; 5:344-66; PMID:1941355; http://dx.doi.org/10.1002/jcla.1860050510
   PubMed Web of Science ®Google Scholar
• Van Dongen GA, Huisman MC, Boellaard R, Harry Hendrikse N, Windhorst AD, Visser GW, Molthoff CF, Vugts DJ. 89Zr-immuno-PET for imaging of long circulating drugs and disease targets: why, how and when to be applied? Q J Nucl Med Mol Imaging 2015; 59:18-38; PMID:25517081
   PubMed Web of Science ®Google Scholar
• Rickert M, Wang X, Boulanger MJ, Goriatcheva N, Garcia KC. The structure of interleukin-2 complexed with its alpha receptor. Science 2005; 308:1477-80; PMID:15933202; http://dx.doi.org/10.1126/science.1109745
   PubMed Web of Science ®Google Scholar
• Wang X, Rickert M, Garcia KC. Structure of the quaternary complex of interleukin-2 with its alpha, beta, gammac receptors. Science 2005; 310:1159-63; PMID:16293754; http://dx.doi.org/10.1126/science.1117893
   PubMed Web of Science ®Google Scholar
• Hilton DJ, Watowich SS, Katz L, Lodish HF. Saturation mutagenesis of the WSXWS motif of the erythropoietin receptor. J Biol Chem 1996; 271:4699-708; PMID:8617735; http://dx.doi.org/10.1074/jbc.271.23.13754
   PubMed Web of Science ®Google Scholar
• Schlothauer T, Herter S, Koller CF, Grau-Richards S, Steinhart V, Spick C, Kubbies M, Klein C, Umana P, Mossner E. Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions. Protein Eng Des Sel 2016; 29(10):457-66; PMID:27578889; http://dx.doi.org/10.1093/protein/gzw040
   PubMed Web of Science ®Google Scholar
• Merchant AM, Zhu Z, Yuan JQ, Goddard A, Adams CW, Presta LG, Carter P. An efficient route to human bispecific IgG. Nat Biotechnol 1998; 16:677-81 PMID: 9661204; PMID:9661204; http://dx.doi.org/10.1038/nbt0798-677
   PubMed Web of Science ®Google Scholar
• Wild N, Andres H, Rollinger W, Krause F, Dilba P, Tacke M, Karl J. A combination of serum markers for the early detection of colorectal cancer. Clin Cancer Res 2010; 16:6111-6121; PMID:20798228; http://dx.doi.org/10.1158/1078-0432.CCR-10-0119
   PubMed Web of Science ®Google Scholar
• Clarke P, Mann J, Simpson JF, Rickard-Dickson K, Primus FJ. Mice transgenic for human carcinoembryonic antigen as a model for immunotherapy. Cancer Res 1998; 58:1469-1477; PMID:9537250
   PubMed Web of Science ®Google Scholar
• Boyman O, Kovar M, Rubinstein MP, Surh CD, Sprent J. Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science 2006; 311:1924-27; PMID:16484453; http://dx.doi.org/10.1126/science.1122927
   PubMed Web of Science ®Google Scholar
• Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, combinations. Sci Transl Med 2016; 8:328rv324; PMID:26936508; http://dx.doi.org/10.1126/scitranslmed.aad7118
   Web of Science ®Google Scholar
• Gerdes CA, Umana P. GA201: a novel humanized and glycoengineered anti-EGFR antibody–response. Clin Cancer Res 2014; 20; 1055; PMID:24536075; http://dx.doi.org/10.1158/1078-0432.CCR-13-2699
   PubMed Web of Science ®Google Scholar
• Spangler JB, Tomala J, Luca VC, Jude KM, Dong S, Ring AM, Votavova P, Pepper M, Kovar M, Garcia KC. Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms. Immunity 2015; 42:815-25; PMID:25992858; http://dx.doi.org/10.1016/j.immuni.2015.04.015
   PubMed Web of Science ®Google Scholar
• Levin AM, Bates DL, Ring AM, Krieg C, Lin JT, Su L, Moraga I, Raeber ME, Bowman GR, Novick P et al. Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’. Nature 2012; 484:529-33; PMID:22446627; http://dx.doi.org/10.1038/nature10975
   PubMed Web of Science ®Google Scholar
• Charych DH, Hoch U, Langowski JL, Lee SR, Addepalli MK, Kirk PB, Sheng DW, Liu XF, Sims PW, VanderVeen LA et al. NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, Marked Efficacy in Mouse Tumor Models. Clinical Cancer Research 2016; 22:680-90; PMID:26832745; http://dx.doi.org/10.1158/1078-0432.CCR-15-1631
   PubMed Web of Science ®Google Scholar
• Gillies SD, Lan Y, Hettmann T, Brunkhorst B, Sun Y, Mueller SO, Lo KM. A low-toxicity IL-2-based immunocytokine retains antitumor activity despite its high degree of IL-2 receptor selectivity. Clin Cancer Res 2011; 17:3673-85; PMID:21531812; http://dx.doi.org/10.1158/1078-0432.CCR-10-2921
   PubMed Web of Science ®Google Scholar
• Gillessen S, Gnad-Vogt US, Gallerani E, Beck J, Sessa C, Omlin A, Mattiacci MR, Liedert B, Kramer D, Laurent J et al. A phase I dose-escalation study of the immunocytokine EMD 521873 (Selectikine) in patients with advanced solid tumours. Eur J Cancer 2013; 49:35-44; PMID:22918078; http://dx.doi.org/10.1016/j.ejca.2012.07.015
   PubMed Web of Science ®Google Scholar
• Carmenate T, Pacios A, Enamorado M, Moreno E, Garcia-Martinez K, Fuente D, Leon K. Human IL-2 mutein with higher antitumor efficacy than wild type IL-2. J Immunol 2013; 190:6230-38; PMID:23677467; http://dx.doi.org/10.4049/jimmunol.1201895
   PubMed Web of Science ®Google Scholar
• Losey HC, Lopes JE, Dean RL, Flick H, Gomes M, Huff MR, Moroso RA, Sun L, Wang C, Waters JF et al. Utilizing a selective agonist of the intermediate-affinity IL-2 receptor with an improved pharmacokinetic profile leads to an enhanced immunostimulatory response with reduced toxicity in mice, Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA). Cancer Res 2015 2001; 75(15 Suppl), Abstract nr 3158.
   Google Scholar
• Sim GC, Liu C, Wang E, Liu H, Creasy C, Dai Z, Overwijk WW, Roszik J, Marincola FM, Hwu P et al. IL-2 variant circumvents ICOS+ regulatory T cell expansion and promotes NK cell activation. Cancer Immunol Res 2016; PMID:27697858; http://dx.doi.org/10.1158/2326-6066.CIR-15-0195
   PubMed Web of Science ®Google Scholar
• Ghasemi R, Lazear E, Wang X, Arefanian S, Zheleznyak A, Carreno BM, Higashikubo R, Gelman AE, Kreisel D, Fremont DH et al. Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy. Nat Commun 2016; 7:12878; PMID:27650575; http://dx.doi.org/10.1038/ncomms12878
   PubMed Web of Science ®Google Scholar
• Boyman O, Surh CD, Sprent J. Potential use of IL-2/anti-IL-2 antibody immune complexes for the treatment of cancer and autoimmune disease. Expert Opin Biol Ther 2006: 6:1323-1331; PMID:17223740; http://dx.doi.org/10.1517/14712598.6.12.1323
   PubMed Web of Science ®Google Scholar
• Arenas-Ramirez N, Zou C, Popp S, Zingg D, Brannetti B, Wirth E, Calzascia T, Kovarik J, Sommer L, Zenke G et al. Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2. Sci Transl Med 2016; 8:367ra166; PMID:27903862; http://dx.doi.org/10.1126/scitranslmed.aag3187
   PubMed Web of Science ®Google Scholar
• Perk LR, Visser GW, Vosjan MJ, Stigter-van Walsum M, Tijink BM, Leemans CR, van Dongen GA. (89)Zr as a PET surrogate radioisotope for scouting biodistribution of the therapeutic radiometals (90)Y and (177)Lu in tumor-bearing nude mice after coupling to the internalizing antibody cetuximab. J Nucl Med 2005; 46:1898-1906; PMID:16269605
   PubMed Web of Science ®Google Scholar
• Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R et al. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nat Immunol 2012; 13:1187-95; PMID:23104097; http://dx.doi.org/10.1038/ni.2449
   PubMed Web of Science ®Google Scholar
• Waldmann TA. The shared and contrasting roles of IL2 and IL15 in the life and death of normal and neoplastic lymphocytes: implications for cancer therapy. Cancer Immunol Res 2015; 3:219-227; PMID:25736261; http://dx.doi.org/10.1158/2326-6066.CIR-15-0009
   PubMed Web of Science ®Google Scholar
• Conlon KC, Lugli E, Welles HC, Rosenberg SA, Fojo AT, Morris JC, Fleisher TA, Dubois SP, Perera LP, Stewart DM et al. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2015; 33:74-82; PMID:25403209; http://dx.doi.org/10.1200/JCO.2014.57.3329
   PubMed Web of Science ®Google Scholar
• Otegbeye F, Mackowski N, Ojo E, De Lima M, Wald DN. The IL-15 Super-Agonist ALT-803 Promotes Superior Activation and Cytotoxicity of Ex Vivo Expanded NK Cells Against AML. Blood 2015; 126:3090.
   Web of Science ®Google Scholar
• Rosario M, Liu B, Kong L, Collins LI, Schneider SE, Chen X, Han K, Jeng EK, Rhode PR, Leong JW et al. The IL-15-Based ALT-803 Complex Enhances FcγRIIIa-Triggered NK Cell Responses and In Vivo Clearance of B Cell Lymphomas. Clin Cancer Res. 2016; 22:596-608; PMID:26423796; http://dx.doi.org/10.1158/1078-0432.CCR-15-1419
   Google Scholar
• Wong HC, Jeng EK, Rhode PR. The IL-15-based superagonist ALT-803 promotes the antigen-independent conversion of memory CD8(+) T cells into innate-like effector cells with antitumor activity. Oncoimmunology 2013; 2:e26442; PMID:24404427; http://dx.doi.org/10.4161/onci.26442
   PubMed Web of Science ®Google Scholar
• Xu WX, Jones M, Liu B, Zhu XY, Johnson CB, Edwards AC, Kong L, Jeng EK, Han KP, Marcus WD et al. Efficacy and Mechanism-of-Action of a Novel Superagonist Interleukin-15: Interleukin-15 Receptor alpha Su/Fc Fusion Complex in Syngeneic Murine Models of Multiple Myeloma. Cancer Res 2013; 73:3075-86; PMID:23644531; http://dx.doi.org/10.1158/0008-5472.CAN-12-2357
   PubMed Web of Science ®Google Scholar
• Miller JS, Cooley S, Holtan S, Arora M, Ustun C, Jeng E, Wong HC, Verneris MR, Wagner JE, Weisdorf DJ et al. 'First-in-human' phase I dose escalation trial of IL-15N72D/IL-15R alpha-Fc superagonist complex (ALT-803) demonstrates immune activation with anti-tumor activity in patients with relapsed hematological malignancy. Blood 2015; 126:1957; http://dx.doi.org/10.1182/blood-2015-02-625574
   Web of Science ®Google Scholar
• Liu B, Kong L, Han K, Hong H, Marcus WD, Chen X, Jeng EK, Alter S, Zhu X, Rubinstein MP et al. A novel fusion of ALT-803 (IL-15 Superagonist) with an antibody demonstrates antigen-specific antitumor responses. J Biol Chem 2016; 291(46):23869-881; PMID:27650494; http://dx.doi.org/10.1074/jbc.M116.733600
   PubMed Web of Science ®Google Scholar
• Yadav M, Jhunjhunwala S, Phung QT, Lupardus P, Tanguay J, Bumbaca S, Franci C, Cheung TK, Fritsche J, Weinschenk T et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 2014; 515:572-6; PMID:25428506; http://dx.doi.org/10.1038/nature14001
   PubMed Web of Science ®Google Scholar
• Lechner MG, Karimi SS, Barry-Holson K, Angell TE, Murphy KA, Church CH, Ohlfest JR, Hu P, Epstein AL. Immunogenicity of murine solid tumor models as a defining feature of in vivo behavior and response to immunotherapy. J Immunother 2013; 36:477-89; PMID:24145359; http://dx.doi.org/10.1097/01.cji.0000436722.46675.4a
   PubMed Web of Science ®Google Scholar
• Schliemann C, Palumbo A, Zuberbuhler K, Villa A, Kaspar M, Trachsel E, Klapper W, Menssen HD, Neri D. Complete eradication of human B-cell lymphoma xenografts using rituximab in combination with the immunocytokine L19-IL2. Blood 2009; 113:2275-83; PMID:19005180; http://dx.doi.org/10.1182/blood-2008-05-160747
   PubMed Web of Science ®Google Scholar