Advances in Immunotherapy for Pancreatic Cancer: 2013

  • Nicholas C DeVito Tufts Medical Center. Boston, MA, USA
  • Muhammad Wasif Saif Tufts Medical Center. Boston, MA, USA
Keywords: Pancreatic Neoplasms, immunotherapy, vaccine, chemoimmunotherapy


Pancreatic cancer is one of the more difficult malignancies to treat, and there is a great need for less toxic, effective regimens. Immunotherapy has shown potential in the treatment of pancreatic cancer, and at ASCO 2013 there were several progressive advances in its clinical application. Abstracts #3067, #3049, #3007, #4040, #LBA4004, and #3090 will be discussed. New developments in the field of immunotherapy are promising novel treatments for pancreatic neoplasms with tolerable side effect profiles.

Image: Detail of immune response pathways induced following cytotoxic therapy.


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Author Biography

Nicholas C DeVito, Tufts Medical Center. Boston, MA, USA

Tufts Medical Center
Department of Internal Medicine
Internal Medicine Resident


Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30. doi: 10.3322/caac.21166; 10.3322/caac.21166.

Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E. and Forman, D. Global cancer statistics. CA: A Cancer Journal for Clinicians, 2011; 61: 69–90.

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. doi: 10.1002/cncr.22852.

Conroy, T., Desseigne, F., Ychou, M., Bouche, O., Guimbaud, R., Becouarn, Y. et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817–1825

Oettle, H., Post, S., Neuhaus, P., Gellert, K., Langrehr, J., Ridwelski, K. et al. Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007; 297: 267–277.

Galili U, Clark MR, Shohet SB, Buehler J, Macher BA. Evolutionary relationship between the natural anti-gal antibody and the gal alpha 1----3Gal epitope in primates. Proc Natl Acad Sci U S A. 1987; 84(5):1369-1373.

Galili U, Shohet SB, Kobrin E, Stults CL, Macher BA. Man, apes, and old world monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem. 1988; 263(33):17755-17762.

Rossi, G., Mautino, M., Awwad, D., Husske, K., Lejukole, H., Koenigsfeld, M. et al. Allogeneic melanoma vaccine expressing alphaGal epitopes induces antitumor immunity to autologous antigens in mice without signs of toxicity. J Immunother 2008; 31: 545–554.

Rossi, G., Mautino, M., Unfer, R., Seregina, T., Vahanian, N. and Link, C. Effective treatment of preexisting melanoma with whole cell vaccines expressing alpha(1,3)-galactosyl epitopes. Cancer Res 2005; 65: 10555–10561.

Rossi, G., Unfer, R., Seregina, T. and Link, C. Complete protection against melanoma in absence of autoimmune depigmentation after rejection of melanoma cells expressing alpha(1,3)galactosyl epitopes. Cancer Immunol Immunother 2005; 54: 999–1009.

Hardacre, J., Mulcahy, M., Small, W., Talamonti, M., Obel, J. and Lima, R. Addition of algenpantucel-L immunotherapy to standard of care (SOC) adjuvant therapy for pancreatic cancer. J Clin Oncol 2012; 30(Suppl.): abstract 4049.

Dranoff, G., Jaffee, E., Lazenby, A., Golumbek, P., Levitsky, H., Brose, K. 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: 3539–3543.

Jaffee, E., Hruban, R., Biedrzycki, B., Laheru, D., Schepers, K., Sauter, P. et al. Novel allogeneic granulocyte-macrophage colony-stimulating factorsecreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. J Clin Oncol 2001; 19: 145–156.

Lutz, E., Yeo, C., Lillemoe, K., Biedrzycki, B., Kobrin, B., Herman, J. 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: 328–335.

Abrams, S., Khleif, S., Bergmann-Leitner, E., Kantor, J., Chung, Y., Hamilton, J. et al. Generation of stable CD4+ and CD8+ T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations. Cell Immunol 1997; 182: 137–151.

Gjertsen, M., Bakka, A., Breivik, J., Saeterdal, I., Solheim, B., Soreide, O. 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: 1399–1400.

Gjertsen, M., Bakka, A., Breivik, J., Saeterdal, I., Gedde-Dahl, T., Stokke, K. 3rd et al. Ex vivo ras peptide vaccination in patients with advanced pancreatic cancer: results of a phase I/II study. Int J Cancer 1996; 65: 450–453.

Carbone, D., Ciernik, I., Kelley, M., Smith, M., Nadaf, S., Kavanaugh, D. et al. Immunization with mutant p53- and K-ras-derived peptides in cancer patients: immune response and clinical outcome. J Clin Oncol 2005; 23: 5099–5107.

Gjertsen, M., Buanes, T., Rosseland, A., Bakka, A., Gladhaug, I., Soreide, O. 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: 441–450.

Vasef, M., Ross, J. and Cohen, M. Telomerase activity in human solid tumors. Diagnostic utility and clinical applications. Am J Clin Pathol 1999; 112(1 Suppl. 1): S68–S75.

Hiyama E, Kodama T, Shinbara K, et al. Telomerase activity is detected in pancreatic cancer but not in benign tumors. Cancer Res. 1997; 57(2):326-331

Mizumoto K, Tanaka M. Detection of telomerase activity in patients with pancreatic cancer. Methods Mol Med. 2005; 103:199-205

Suehara, N., Mizumoto, K., Kusumoto, M., Niiyama, H., Ogawa, T., Yamaguchi, K. et al. Telomerase activity detected in pancreatic juice 19 months before a tumor is detected in a patient with pancreatic cancer. Am J Gastroenterol 1998; 93: 1967–1971.

Kyte JA. Cancer vaccination with telomerase peptide GV1001. Expert Opin Investig Drugs. 2009;18(5):687-694.

Bernhardt, S., Gjertsen, M., Trachsel, S., Moller, M., Eriksen, J., Meo, M. et al. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study. Br J Cancer 2006; 95: 1474–1482.

Middleton GW, Valle JW, Wadsley J, Propper D, Coxon FY, Ross PJ, et al. A phase III randomized trial of chemoimmunotherapy comprising gemcitabine and capecitabine with or without telomerase vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer. J Clin Oncol 2103; 31(Suppl.): Abstract #LBA4004.

Kaufman, H., Kim-Schulze, S., Manson, K., DeRaffele, G., Mitcham, J., Seo, K. et al. Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer. J Transl Med 2007; 5: 60.

Leuchtenberger M. Therion Biologics Corporation Reports Results of Phase 3 PANVAC-VF Trial and Announces Plans for Company Sale. BioSpace, Inc., Centennial, CO, USA;2006 (Accessed June 6th, 2013. therion-biologics-corporation-reports-results-of/23073

Madan RA, Arlen PM, Gulley JL. PANVAC-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma. Expert Opin Biol Ther. 2007 Apr;7(4):543-54.

Zhu, K., Qin, H., Cha, S., Neelapu, S., Overwijk, W., Lizee, G. et al. Survivin DNA vaccine generated specific antitumor effects in pancreatic carcinoma and lymphoma mouse models. Vaccine 2007; 25: 7955–7961.

Wobser, M., Keikavoussi, P., Kunzmann, V., Weininger, M., Andersen, M. and Becker, J. 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: 1294–1298.

Kimura, Y., Tsukada, J., Tomoda, T., Takahashi, H., Imai, K., Shimamura, K. et al. Clinical and immunologic evaluation of dendritic cell-based immunotherapy in combination with gemcitabine and/ or S-1 in patients with advanced pancreatic carcinoma. Pancreas 2012; 41: 195–205.

Morse, M., Nair, S., Boczkowski, D., Tyler, D., Hurwitz, H., Proia, A. 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: 1–6.

Pecher, G., Haring, A., Kaiser, L. and Thiel, E. Mucin gene (MUC1) transfected dendritic cells as vaccine: results of a phase I/II clinical trial. Cancer Immunol Immunother 2002; 51: 669–673.

Ramanathan, R., Lee, K., McKolanis, J., Hitbold, E., Schraut, W., Moser, A. et al. Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. Cancer Immunol Immunother 2005; 54: 254–264.

Rong, Y., Qin, X., Jin, D., Lou, W., Wu, L., Wang, D. et al. A phase I pilot trial of MUC1-peptidepulsed dendritic cells in the treatment of advanced pancreatic cancer. Clin Exp Med 2012; 12: 173–180.

Oki, Y. and Younes, A. Heat shock protein based cancer vaccines. Expert Rev Vaccines 2004; 3: 403–411.

Maki, R., Livingston, P., Lewis, J., Janetzki, S., Klimstra, D., Desantis, D. et al. A phase I pilot study of autologous heat shock protein vaccine HSPPC-96 in patients with resected pancreatic adenocarcinoma. Dig Dis Sci 2007; 52: 1964–1972.

Schmitz-Winnenthal FH, Grenacher L, Friedrich T, Lubenau H, Springer M, Breiner KM, et al. VXM01, an oral T-cell vaccine targeting the tumor vasculature: Results from a randomized, controlled, first-in-man study in pancreatic cancer patients. J Clin Oncol 2103; 31(Suppl.): Abstract #3090.

Bae J, Carrasco R, Daley J, Dranoff G, Anderson KC, Munshi NC. Novel heteroclitic XBP1 peptides evoking antigen-specific cytotoxic T lymphocytes targeting various solid tumors. J Clin Oncol 2103; 31(Suppl.): Abstract #3067.

Chai K, Ai YQ, Jiang TW. Phase II study of dendritic cell vaccination combined with recombinant adenovirus-p53 in treatment for patients with advanced pancreatic carcinoma. J Clin Oncol 2103; 31(Suppl.): Abstract #3049.

Rossi GR, Hardacre JM, Mulcahy MF, Talamonti MS, Obel JC, Rocha Lima CMS, et al. Effect of algenpantucel-L immunotherapy for pancreatic cancer on anti-mesothelin antibody (Ab) titers and correlation with improved overall survival. J Clin Oncol 2103; 31(Suppl.): Abstract #3007.

Le DT, Wang-Gillam A, Picozzi VJ, Greten TF, Crocenzi TS, Springett GM, et al. Interim safety and efficacy analysis of a phase II, randomized study of GVAX pancreas and CRS-207 immunotherapy in patients with metastatic pancreatic cancer. J Clin Oncol 2103; 31(Suppl.): Abstract #4040.

Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005; 11(18):6713-6721.

Ghansah T, Vohra N, Kinney K, et al. Dendritic cell immunotherapy combined with gemcitabine chemotherapy enhances survival in a murine model of pancreatic carcinoma. Cancer Immunol Immunother. 2013; 62(6):1083-1091. doi: 10.1007/s00262-013-1407-9; 10.1007/s00262-013-1407-9.

Plate JM, Plate AE, Shott S, Bograd S, Harris JE. Effect of gemcitabine on immune cells in subjects with adenocarcinoma of the pancreas. Cancer Immunol Immunother. 2005; 54(9):915-925.

Shiao SL, Ganesan AP, Rugo HS, Coussens LM. Immune microenvironments in solid tumors: New targets for therapy. Genes Dev. 2011; 25(24):2559-2572.

Hassan R, Ho M. Mesothelin targeted cancer immunotherapy. Eur J Cancer. 2008 Jan; 44(1):46-53.

Le DT, Brockstedt DG, Nir-Paz R, et al. A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction. Clin Cancer Res. 2012 Feb 1;18(3):858-68

Rettig L, Seidenberg S, Parvanova I, Samaras P, Curioni A, Knuth A, Pascolo S. Gemcitabine depletes regulatory T-cells in human and mice and enhances triggering of vaccine-specific cytotoxic T-cells. Int J Cancer. 2011 Aug 15;129(4):832-8.

Williams S,C.P. No end in sight for telomerase-targeted cancer drugs. Nature Medicine 2013; 19,6

Adams, S. Toll-like receptor agonists in cancer therapy Immunotherapy. 2009 November 1; 1(6): 949–964.

Royal RE, Levy C, Turner K et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010 Oct; 33(8):828-33.

Otahal P, Knowles BB, Tevethia SS, Schell TD. Anti-CD40 conditioning enhances the T(CD8) response to a highly tolerogenic epitope and subsequent immunotherapy of simian virus 40 T antigen-induced pancreatic tumors. J Immunol. 2007 Nov 15; 179(10):6686-95.

Khong A, Nelson DJ, Nowak AK, Lake RA, Robinson BW. The use of agonistic anti-CD40 therapy in treatments for cancer. Int Rev Immunol. 2012 Aug; 31(4):246-66.

Meili Zhang, Zhengsheng Yao, Sigrid Dubois, Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer PNAS 2009; 106 (18) 7513-7518

Jedd D. Wolchok, M.D., Ph.D., Harriet Kluger, M.D., et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013 Jun 2.

Detail of immune response pathways induced following cytotoxic therapy
How to Cite
DeVitoN., & SaifM. (2013). Advances in Immunotherapy for Pancreatic Cancer: 2013. JOP. Journal of the Pancreas, 14(4), 347-353.
Highlights from the “2013 ASCO Annual Meeting”. Chicago, IL, USA. May 31 - June 4, 2013

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