Pancreatic cancer vaccine: a unique potential therapy

References

• Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–2921.
   PubMed Web of Science ®Google Scholar
• Becker AE, Hernandez YG, Frucht H, Lucas AL. Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection. World J Gastroenterol. 2014;20(32):11182–11198.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.
   PubMed Web of Science ®Google Scholar
• Bilimoria KY, Bentrem DJ, Ko CY, et al. Validation of the 6th edition AJCC pancreatic cancer staging system: report from the National Cancer Database. Cancer. 2007;110(4):738–744.
   PubMed Web of Science ®Google Scholar
• Distler M, Aust D, Weitz J, Pilarsky C, Grutzmann R. Precursor lesions for sporadic pancreatic cancer: PanIN, IPMN, and MCN. Biomed Res Int. 2014;2014:474905.
   PubMed Web of Science ®Google Scholar
• Hruban RH, Adsay NV, Albores-Saavedra J, et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol. 2001;25(5):579–586.
   PubMed Web of Science ®Google Scholar
• Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28(8):977–987.
   PubMed Web of Science ®Google Scholar
• Macgregor-Das AM, Iacobuzio-Donahue CA. Molecular pathways in pancreatic carcinogenesis. J Surg Oncol. 2013;107(1):8–14.
   Web of Science ®Google Scholar
• Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378(9791):607–620.
   PubMed Web of Science ®Google Scholar
• Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321(5897):1801–1806.
   PubMed Web of Science ®Google Scholar
• van Heek NT, Meeker AK, Kern SE, et al. Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am J Pathol. 2002;161(5):1541–1547.
   PubMed Web of Science ®Google Scholar
• Garrido-Laguna I, Hidalgo M. Pancreatic cancer: from state-of-the-art treatments to promising novel therapies. Nat Rev Clin Oncol. 2015;12(6):319–334.
   PubMed Web of Science ®Google Scholar
• Rossi ML, Rehman AA, Gondi CS. Therapeutic options for the management of pancreatic cancer. World J Gastroenterol. 2014;20(32):11142–11159.
   PubMed Web of Science ®Google Scholar
• Stathis A, Moore MJ. Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol. 2010;7(3):163–172.
   PubMed Web of Science ®Google Scholar
• Wolfgang CL, Herman JM, Laheru DA, et al. Recent progress in pancreatic cancer. CA Cancer J Clin. 2013;63(5):318–348.
   PubMed Web of Science ®Google Scholar
• Harsha HC, Kandasamy K, Ranganathan P, et al. A compendium of potential biomarkers of pancreatic cancer. PLoS Med. 2009;6(4):e1000046.
   PubMed Web of Science ®Google Scholar
• Chung MH, Gupta RK, Bilchik AJ, Ye W, Yee R, Morton DL. Preoperative serum TA90-IC as an adjunct to serum CA 19-9 in the diagnosis of pancreatic malignancy: a pilot study. Curr Surg. 2002;59(2):194–198.
   Google Scholar
• Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol. 2007;33(3):266–270.
   PubMed Web of Science ®Google Scholar
• Berger AC, Garcia M Jr, Hoffman JP, et al. Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol. 2008;26(36):5918–5922.
   PubMed Web of Science ®Google Scholar
• Halm U, Schumann T, Schiefke I, Witzigmann H, Mössner J, Keim V. Decrease of CA 19-9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer. Br J Cancer. 2000;82(5):1013–1016.
   PubMed Web of Science ®Google Scholar
• Ishii H, Okada S, Sato T, et al. CA 19-9 in evaluating the response to chemotherapy in advanced pancreatic cancer. Hepatogastroenterology. 1997;44(13):279–283.
   PubMedGoogle Scholar
• Montgomery RC, Hoffman JP, Riley LB, Rogatko A, Ridge JA, Eisenberg BL. Prediction of recurrence and survival by post-resection CA 19-9 values in patients with adenocarcinoma of the pancreas. Ann Surg Oncol. 1997;4(7):551–556.
   Web of Science ®Google Scholar
• Wong D, Ko AH, Hwang J, Venook AP, Bergsland EK, Tempero MA. Serum CA19-9 decline compared to radiographic response as a surrogate for clinical outcomes in patients with metastatic pancreatic cancer receiving chemotherapy. Pancreas. 2008;37(3):269–274.
   PubMed Web of Science ®Google Scholar
• Frebourg T, Bercoff E, Manchon N, et al. The evaluation of CA 19-9 antigen level in the early detection of pancreatic cancer. A prospective study of 866 patients. Cancer. 1988;62(11):2287–2290.
   Web of Science ®Google Scholar
• Capello M, Cappello P, Linty FC, et al. Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models. J Hematol Oncol. 2013;6:67.
   PubMed Web of Science ®Google Scholar
• Tomaino B, Cappello P, Capello M, et al. Circulating autoantibodies to phosphorylated alpha-enolase are a hallmark of pancreatic cancer. J Proteome Res. 2011;10(1):105–112.
   Web of Science ®Google Scholar
• Melo SA, Luecke LB, Kahlert C, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015;523(7559):177–182.
   PubMed Web of Science ®Google Scholar
• Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004;363(9414):1049–1057.
   PubMed Web of Science ®Google Scholar
• Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Büchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004; 91(5):586–594.
   Web of Science ®Google Scholar
• Riediger H, Keck T, Wellner U, et al. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg. 2009;13(7):1337–1344.
   Web of Science ®Google Scholar
• Wasif N, Ko CY, Farrell J, et al. Impact of tumor grade on prognosis in pancreatic cancer: should we include grade in AJCC staging? Ann Surg Oncol. 2010;17(9):2312–2320.
   Web of Science ®Google Scholar
• Fortner JG, Klimstra DS, Senie RT, Maclean BJ. Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy. Ann Surg. 1996;223(2):147–153.
   Web of Science ®Google Scholar
• Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362(17):1605–1617.
   PubMed Web of Science ®Google Scholar
• Maitra A, Hruban RH. Pancreatic cancer. Annu Rev Pathol. 2008;3:157–188.
   PubMed Web of Science ®Google Scholar
• Tian H, Callahan CA, DuPree KJ, et al. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci U S A. 2009;106(11):4254–4259.
   PubMed Web of Science ®Google Scholar
• Dineen SP, Roland CL, Greer R, et al. Smac mimetic increases chemotherapy response and improves survival in mice with pancreatic cancer. Cancer Res. 2010;70(7):2852–2861.
   Web of Science ®Google Scholar
• Hwang JH, Voortman J, Giovannetti E, et al. Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. PLoS One. 2010;5(5):e10630.
   PubMed Web of Science ®Google Scholar
• Harikumar KB, Kunnumakkara AB, Sethi G, et al. Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer. 2010;127(2):257–268.
   PubMed Web of Science ®Google Scholar
• Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009;27(33):5513–5518.
   PubMed Web of Science ®Google Scholar
• Banerjee S, Kaseb AO, Wang Z, et al. Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res. 2009;69(13):5575–5583.
   Web of Science ®Google Scholar
• Baylot V, Andrieu C, Katsogiannou M, et al. OGX-427 inhibits tumor progression and enhances gemcitabine chemotherapy in pancreatic cancer. Cell Death Dis. 2011;2:e221.
   PubMed Web of Science ®Google Scholar
• Kanai M, Yoshimura K, Asada M, et al. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol. 2011;68(1):157–164.
   PubMed Web of Science ®Google Scholar
• Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7(4):e1000267.
   PubMed Web of Science ®Google Scholar
• Lemmens VE, Bosscha K, van der Schelling G, Brenninkmeijer S, Coebergh JW, de Hingh IH. Improving outcome for patients with pancreatic cancer through centralization. Br J Surg. 2011;98(10):1455–1462.
   Web of Science ®Google Scholar
• Massucco P, Capussotti L, Magnino A, et al. Pancreatic resections after chemoradiotherapy for locally advanced ductal adenocarcinoma: analysis of perioperative outcome and survival. Ann Surg Oncol. 2006; 13(9):1201–1208.
   PubMed Web of Science ®Google Scholar
• Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997; 15(6):2403–2413.
   PubMed Web of Science ®Google Scholar
• Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364(19):1817–1825.
   PubMed Web of Science ®Google Scholar
• Moore MJ, Goldstein D, Hamm J, et al; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(15):1960–1966.
   PubMed Web of Science ®Google Scholar
• Wang JP, Wu CY, Yeh YC, et al. Erlotinib is effective in pancreatic cancer with epidermal growth factor receptor mutations: a randomized, open-label, prospective trial. Oncotarget. 2015;6(20):18162–18173.
   PubMed Web of Science ®Google Scholar
• Edmonds C, Cengel KA. Tumor-stroma interactions in pancreatic cancer: will this SPARC prove a raging fire? Cancer Biol Ther. 2008; 7(11):1816–1817.
   Web of Science ®Google Scholar
• Infante JR, Matsubayashi H, Sato N, et al. Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol. 2007;25(3):319–325.
   PubMed Web of Science ®Google Scholar
• Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–1703.
   PubMed Web of Science ®Google Scholar
• Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014–1022.
   PubMed Web of Science ®Google Scholar
• Jobin C. Colorectal cancer: looking for answers in the microbiota. Cancer Discov. 2013;3(4):384–387.
   Web of Science ®Google Scholar
• Clark CE, Beatty GL, Vonderheide RH. Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer Lett. 2009;279(1):1–7.
   Web of Science ®Google Scholar
• Guerra C, Collado M, Navas C, et al. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell. 2011;19(6):728–739.
   PubMed Web of Science ®Google Scholar
• Gregory AD, Houghton AM. Tumor-associated neutrophils: new targets for cancer therapy. Cancer Res. 2011;71(7):2411–2416.
   PubMed Web of Science ®Google Scholar
• Sparmann A, Bar-Sagi D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell. 2004;6(5):447–458.
   PubMed Web of Science ®Google Scholar
• Beatty GL, Chiorean EG, Fishman MP, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011;331(6024):1612–1616.
   PubMed Web of Science ®Google Scholar
• Beatty GL, Winograd R, Evans RA, et al. Exclusion of T cells from pancreatic carcinomas in mice is regulated by Ly6C(low) F4/80(+) extratumoral macrophages. Gastroenterology. 2015;149(1):201–210.
   PubMed Web of Science ®Google Scholar
• Mitchem JB, Brennan DJ, Knolhoff BL, et al. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. 2013;73(3):1128–1141.
   PubMed Web of Science ®Google Scholar
• Qian BZ, Li J, Zhang H, et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011;475(7355):222–225.
   PubMed Web of Science ®Google Scholar
• Kitamura T, Qian BZ, Soong D, et al. CCL2-induced chemokine cascade promotes breast cancer metastasis by enhancing retention of metastasis-associated macrophages. J Exp Med. 2015;212(7):1043–1059.
   PubMed Web of Science ®Google Scholar
• Zhu Y, Knolhoff BL, Meyer MA, et al. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 2014;74(18):5057–5069.
   PubMed Web of Science ®Google Scholar
• Pyonteck SM, Akkari L, Schuhmacher AJ, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013;19(10):1264–1272.
   PubMed Web of Science ®Google Scholar
• Bayne LJ, Beatty GL, Jhala N, et al. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell. 2012;21(6):822–835.
   PubMed Web of Science ®Google Scholar
• Stromnes IM, Brockenbrough JS, Izeradjene K, et al. Targeted depletion of an MDSC subset unmasks pancreatic ductal adenocarcinoma to adaptive immunity. Gut. 2014;63(11):1769–1781.
   PubMed Web of Science ®Google Scholar
• Pylayeva-Gupta Y, Lee KE, Hajdu CH, Miller G, Bar-Sagi D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell. 2012;21(6):836–847.
   PubMed Web of Science ®Google Scholar
• Apte MV, Wilson JS, Lugea A, Pandol SJ. A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology. 2013;144(6):1210–1219.
   PubMed Web of Science ®Google Scholar
• Feig C, Jones JO, Kraman M, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A. 2013;110(50):20212–20217.
   PubMed Web of Science ®Google Scholar
• Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009;324(5933):1457–1461.
   PubMed Web of Science ®Google Scholar
• Özdemir BC, Pentcheva-Hoang T, Carstens JL, et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014;25(6):719–734.
   PubMed Web of Science ®Google Scholar
• Rhim AD, Oberstein PE, Thomas DH, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25(6):735–747.
   PubMed Web of Science ®Google Scholar
• Gore J, Korc M. Pancreatic cancer stroma: friend or foe? Cancer Cell. 2014;25(6):711–712.
   PubMed Web of Science ®Google Scholar
• Fukunaga A, Miyamoto M, Cho Y, et al. CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas. 2004;28(1):e26–e31.
   PubMed Web of Science ®Google Scholar
• Fogar P, Sperti C, Basso D, et al. Decreased total lymphocyte counts in pancreatic cancer: an index of adverse outcome. Pancreas. 2006;32(1):22–28.
   PubMed Web of Science ®Google Scholar
• Emmrich J, Sparmann G, Hopt U, Lohr M, Liebe S. Typing of leukocytes in pancreatic tissue surrounding human pancreatic carcinoma. Ann N Y Acad Sci. 1999;880:171–174.
   Web of Science ®Google Scholar
• Ademmer K, Ebert M, Müller-Ostermeyer F, et al. Effector T lymphocyte subsets in human pancreatic cancer: detection of CD8+CD18+ cells and CD8+CD103+ cells by multi-epitope imaging. Clin Exp Immunol. 1998;112(1):21–26.
   Web of Science ®Google Scholar
• Amedei A, Niccolai E, Benagiano M, et al. Ex vivo analysis of pancreatic cancer-infiltrating T lymphocytes reveals that ENO-specific Tregs accumulate in tumor tissue and inhibit Th1/Th17 effector cell functions. Cancer Immunol Immunother. 2013;62(7):1249–1260.
   PubMed Web of Science ®Google Scholar
• Rossi GR, Mautino MR, Unfer RC, Seregina TM, Vahanian N, Link CJ. Effective treatment of preexisting melanoma with whole cell vaccines expressing alpha(1,3)-galactosyl epitopes. Cancer Res. 2005;65(22):10555–10561.
   PubMed Web of Science ®Google Scholar
• Gunturu KS, Rossi GR, Saif MW. Immunotherapy updates in pancreatic cancer: are we there yet? Ther Adv Med Oncol. 2013;5(1):81–89.
   PubMed Web of Science ®Google Scholar
• Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A. 1993;90(8):3539–3543.
   PubMed Web of Science ®Google Scholar
• Jaffee EM, Hruban RH, Biedrzycki B, et al. Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. J Clin Oncol. 2001;19(1):145–156.
   PubMed Web of Science ®Google Scholar
• Lutz E, Yeo CJ, Lillemoe KD, et al. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A phase II trial of safety, efficacy, and immune activation. Ann Surg. 2011;253(2):328–335.
   PubMed Web of Science ®Google Scholar
• Gjertsen MK, Bakka A, Breivik J, et al. Vaccination with mutant ras peptides and induction of T-cell responsiveness in pancreatic carcinoma patients carrying the corresponding RAS mutation. Lancet. 1995;346(8987):1399–1400.
   PubMed Web of Science ®Google Scholar
• Gjertsen MK, Buanes T, Rosseland AR, et al. Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: clinical and immunological responses in patients with pancreatic adenocarcinoma. Int J Cancer. 2001;92(3):441–450.
   PubMed Web of Science ®Google Scholar
• Wobser M, Keikavoussi P, Kunzmann V, Weininger M, Andersen MH, Becker JC. Complete remission of liver metastasis of pancreatic cancer under vaccination with a HLA-A2 restricted peptide derived from the universal tumor antigen survivin. Cancer Immunol Immunother. 2006;55(10):1294–1298.
   PubMed Web of Science ®Google Scholar
• Staff C, Mozaffari F, Frodin JE, Mellstedt H, Liljefors M. Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients. Int J Oncol. 2014;45(3):1293–1303.
   Web of Science ®Google Scholar
• Middleton G, Silcocks P, Cox T, et al. Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. Lancet Oncol. 2014;15(8):829–840.
   PubMed Web of Science ®Google Scholar
• Marshall JL, Gulley JL, Arlen PM, et al. Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas. J Clin Oncol. 2005;23(4):720–731.
   PubMed Web of Science ®Google Scholar
• Madan RA, Bilusic M, Heery C, Schlom J, Gulley JL. Clinical evaluation of TRICOM vector therapeutic cancer vaccines. Semin Oncol. 2012;39(3):296–304.
   PubMed Web of Science ®Google Scholar
• Morse MA, Nair SK, Boczkowski D, et al. The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer. Int J Gastrointest Cancer. 2002;32(1):1–6.
   PubMedGoogle Scholar
• Rong Y, Qin X, Jin D, et al. A phase I pilot trial of MUC1-peptide-pulsed dendritic cells in the treatment of advanced pancreatic cancer. Clin Exp Med. 2012;12(3):173–180.
   PubMed Web of Science ®Google Scholar
• Shindo Y, Hazama S, Maeda Y, et al. Adoptive immunotherapy with MUC1-mRNA transfected dendritic cells and cytotoxic lymphocytes plus gemcitabine for unresectable pancreatic cancer. J Transl Med. 2014;12:175.
   PubMed Web of Science ®Google Scholar
• Muminova ZE, Strong TV, Shaw DR. Characterization of human mesothelin transcripts in ovarian and pancreatic cancer. BMC Cancer. 2004;4:19.
   PubMed Web of Science ®Google Scholar
• Laheru D, Lutz E, Burke J, et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res. 2008;14(5):1455–1463.
   PubMed Web of Science ®Google Scholar
• Le DT, Wang-Gillam A, Picozzi V, et al. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015;33(12):1325–1333.
   PubMed Web of Science ®Google Scholar
• Nishida S, Koido S, Takeda Y, et al. Wilms tumor gene (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer. J Immunother. 2014;37(2):105–114.
   PubMed Web of Science ®Google Scholar
• Gjerstorff MF, Andersen MH, Ditzel HJ. Oncogenic cancer/testis antigens: prime candidates for immunotherapy. Oncotarget. 2015; 6(18):15772–15787.
   PubMedGoogle Scholar
• Okuyama R, Aruga A, Hatori T, Takeda K, Yamamoto M. Immunological responses to a multi-peptide vaccine targeting cancer-testis antigens and VEGFRs in advanced pancreatic cancer patients. Oncoimmunology. 2013;2(11):e27010.
   Web of Science ®Google Scholar
• Le DT, Lutz E, Uram JN, et al. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother. 2013;36(7):382–389.
   PubMed Web of Science ®Google Scholar
• Wang Z, Troilo PJ, Wang X, et al. Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation. Gene Ther. 2004;11(8):711–721.
   PubMed Web of Science ®Google Scholar
• Tomaino B, Cappello P, Capello M, et al. Autoantibody signature in human ductal pancreatic adenocarcinoma. J Proteome Res. 2007; 6(10):4025–4031.
   PubMed Web of Science ®Google Scholar
• Cappello P, Tomaino B, Chiarle R, et al. An integrated humoral and cellular response is elicited in pancreatic cancer by alpha-enolase, a novel pancreatic ductal adenocarcinoma-associated antigen. Int J Cancer. 2009;125(3):639–648.
   PubMed Web of Science ®Google Scholar
• Principe M, Ceruti P, Shih NY, et al. Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells. Oncotarget. 2015;6(13):11098–11113.
   Google Scholar
• Capello M, Ferri-Borgogno S, Cappello P, Novelli F. Alpha-enolase: a promising therapeutic and diagnostic tumor target. FEBS J. 2011;278(7):1064–1074.
   Web of Science ®Google Scholar
• Cappello P, Rolla S, Chiarle R, et al. Vaccination with ENO1 DNA prolongs survival of genetically engineered mice with pancreatic cancer. Gastroenterology. 2013;144(5):1098–1106.
   Web of Science ®Google Scholar
• Castino GF, Cortese N, Capretti G, et al. Spatial distribution of B cells predicts prognosis in human pancreatic adenocarcinoma. OncoImunology. Epub 2015 Sep 11.
   Google Scholar
• Galluzzi L, Senovilla L, Zitvogel L, Kroemer G. The secret ally: immunostimulation by anticancer drugs. Nat Rev Drug Discov. 2012;11(3):215–233.
   PubMed Web of Science ®Google Scholar
• Beatty GL, Torigian DA, Chiorean EG, et al. A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Clin Cancer Res. 2013;19(22):6286–6295.
   PubMed Web of Science ®Google Scholar
• Germano G, Frapolli R, Belgiovine C, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013; 23(2):249–262.
   PubMed Web of Science ®Google Scholar