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Therapeutic Cancer Vaccines

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Immunotherapy for Gastrointestinal Cancer

Abstract

Immune therapy for cancer has evolved significantly in the past several decades. With the recent dramatic successes of novel immune modulating agents in certain cancers, the scientific community has redoubled efforts to expand the impact of these treatments for more patients. Cancer vaccines have been developed and tested in gastrointestinal (GI) cancers for more than two decades, mostly with little success. As a result, there has been little interest or investment in this field of research. However, now that opportunities for combination immune therapies have become more attractive, having an understanding of the past work in cancer vaccines is critical (Fig. 3.1). In this chapter, we will review the most important and representative results of cancer vaccine research in GI cancers. The fundamentals of this work will not only serve future GI cancer research, but also other tumour types.

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References

  1. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480:480–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Matzinger P. The danger model: a renewed sense of self. Science. 2002;296:301–5.

    Article  CAS  PubMed  Google Scholar 

  3. Reis e Sousa C. Dendritic cells in a mature age. Nat Rev Immunol. 2006;6:476–83.

    Article  CAS  PubMed  Google Scholar 

  4. Kapsenberg ML. Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol. 2003;3:984–93.

    Article  CAS  PubMed  Google Scholar 

  5. Langenkamp A, Messi M, Lanzavecchia A, Sallusto F. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat Immunol. 2000;1:311–6.

    Article  CAS  PubMed  Google Scholar 

  6. Wang JY, Wang YH, Jao SW, et al. Molecular mechanisms underlying the tumorigenesis of colorectal adenomas: correlation to activated K-ras oncogene. Oncol Rep. 2006;16:1245–52.

    CAS  PubMed  Google Scholar 

  7. Eser S, Schnieke A, Schneider G, Saur D. Oncogenic KRAS signalling in pancreatic cancer. Br J Cancer. 2014;111:817–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Van Cutsem E, Lenz HJ, Kohne CH, et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015;33:692–700.

    Article  PubMed  CAS  Google Scholar 

  9. Douillard JY, Siena S, Cassidy J, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25:1346–55.

    Article  CAS  PubMed  Google Scholar 

  10. Knudsen ES, O’Reilly EM, Brody JR, Witkiewicz AK. Genetic diversity of pancreatic ductal adenocarcinoma and opportunities for precision medicine. Gastroenterology. 2016;150:48–63.

    Article  PubMed  Google Scholar 

  11. Witkiewicz AK, McMillan EA, Balaji U, et al. Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat Commun. 2015;6:6744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hartley ML, Bade NA, Prins PA, Ampie L, Marshall JL. Pancreatic cancer, treatment options, and GI-4000. Hum Vaccin Immunother. 2015;11:931–7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Muscarella P, Wilfong LS, Ross SB, et al. A randomized, placebo-controlled, double blind, multicenter phase II adjuvant trial of the efficacy, immunogenicity, and safety of GI-4000 plus gem versus gem alone in patients with resected pancreas cancer with activating RAS mutations/survival and immunology analysis of the R1 subgroup. J Clin Oncol. 2012;30:abstr e14501.

    Google Scholar 

  14. Coeshott C, Holmes T, Mattson A, et al. Immune responses to mutated Ras – development of a yeast-based immunotherapeutic. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: from biology to therapy; Lake Buena Vista/ Philadelphia; 2014: AACR. Mol Cancer Res 2014;12:Abstract nr A28.

    Google Scholar 

  15. Gold P, Goldenberg N. The carcinoembryonic antigen (CEA): past, present, and future. McGill J Med. 1997;3:46–66.

    Google Scholar 

  16. Kaufman HL, Schlom J. Vaccines for colon cancer. In: Stern P, Beverly P, Carroll M, editors. Cancer vaccines and immunotherapy. Cambridge: Cambridge University Press; 2000. p. 107–34.

    Chapter  Google Scholar 

  17. Schlom J. Carcinoembryonic antigen (CEA) peptides and vaccines for carcinoma. In: Kast M, editor. Peptide-based cancer vaccines. Austin: Landes Bioscience; 2000. p. 90–105.

    Google Scholar 

  18. Berinstein NL. Carcinoembryonic antigen as a target for therapeutic anticancer vaccines: a review. J Clin Oncol. 2002;20:2197–207.

    Article  CAS  PubMed  Google Scholar 

  19. Tsang KY, Zhu M, Nieroda CA, et al. Phenotypic stability of a cytotoxic T-cell line directed against an immunodominant epitope of human carcinoembryonic antigen. Clin Cancer Res. 1997;3:2439–49.

    CAS  PubMed  Google Scholar 

  20. Zaremba S, Barzaga E, Zhu M, Soares N, Tsang KY, Schlom J. Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen. Cancer Res. 1997;57:4570–7.

    CAS  PubMed  Google Scholar 

  21. Foon KA, John WJ, Chakraborty M, et al. Clinical and immune responses in advanced colorectal cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. Clin Cancer Res. 1997;3:1267–76.

    CAS  PubMed  Google Scholar 

  22. Foon KA, John WJ, Chakraborty M, et al. Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. J Clin Oncol. 1999;17:2889–5.

    CAS  PubMed  Google Scholar 

  23. Bhatnagar A, Carmichael J, Cosgriff T, et al. A randomized, double-blind, placebo controlled phase III study of monoclonal antibody 3H1 plus 5-fluorouracil (5-FU)/leucovorin (LV) in stage IV colorectal carcinoma. Proc Am Soc Clin Oncol. 2003;22:Abstr 1041.

    Google Scholar 

  24. Posner MC, Niedzwiecki D, Venook AP, et al. A phase II prospective multi-institutional trial of adjuvant active specific immunotherapy following curative resection of colorectal cancer hepatic metastases: cancer and leukemia group B study 89903. Ann Surg Oncol. 2008;15:158–64.

    Article  PubMed  Google Scholar 

  25. Geynisman DM, Zha Y, Kunnavakkam R, et al. A randomized phase I study of modified carcinoembryonic antigen (CEA) peptide (CAP1-6D)/montanide/GM-CSF vaccine (CEA-vac) in patients (pts) with pancreatic adenocarcinoma (PC). J Clin Oncol. 2012;30:abstr 2561.

    Google Scholar 

  26. Finn OJ, Jerome KR, Henderson RA, et al. MUC-1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol Rev. 1995;145:61–89.

    Article  CAS  PubMed  Google Scholar 

  27. Goydos JS, Elder E, Whiteside TL, Finn OJ, Lotze MT. A phase I trial of a synthetic mucin peptide vaccine. Induction of specific immune reactivity in patients with adenocarcinoma. J Surg Res. 1996;63:298–304.

    Article  CAS  PubMed  Google Scholar 

  28. Karanikas V, Hwang LA, Pearson J, et al. Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein. J Clin Invest. 1997;100:2783–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Karanikas V, Thynne G, Mitchell P, et al. Mannan mucin-1 peptide immunization: influence of cyclophosphamide and the route of injection. J Immunother. 2001;24:172–83.

    Article  CAS  Google Scholar 

  30. Kimura T, McKolanis JR, Dzubinski LA, et al. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res (Phila). 2013;6:18–26.

    Article  CAS  Google Scholar 

  31. Yang D, Nakao M, Shichijo S, et al. Identification of a gene coding for a protein possessing shared tumor epitopes capable of inducing HLA-A24-restricted cytotoxic T lymphocytes in cancer patients. Cancer Res. 1999;59:4056–63.

    CAS  PubMed  Google Scholar 

  32. Ito M, Shichijo S, Miyagi Y, et al. Identification of SART3-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with different HLA-A2 subtypes. Int J Cancer. 2000;88:633–9.

    Article  CAS  PubMed  Google Scholar 

  33. Suefuji Y, Sasatomi T, Shichijo S, et al. Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in breast cancer patients. Br J Cancer. 2001;84:915–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sasatomi T, Suefuji Y, Matsunaga K, et al. Expression of tumor rejection antigens in colorectal carcinomas. Cancer. 2002;94:1636–41.

    Article  PubMed  Google Scholar 

  35. Miyagi Y, Imai N, Sasatomi T, et al. Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination with SART3 peptides. Clin Cancer Res. 2001;7:3950–62.

    CAS  PubMed  Google Scholar 

  36. Pierce JG, Parsons TF. Glycoprotein hormones: structure and function. Annu Rev Biochem. 1981;50:465–95.

    Article  CAS  PubMed  Google Scholar 

  37. Braunstein GD, Vaitukaitis JL, Carbone PP, Ross GT. Ectopic production of human chorionic gonadotrophin by neoplasms. Ann Intern Med. 1973;78:39–45.

    Article  CAS  PubMed  Google Scholar 

  38. Lundin M, Nordling S, Lundin J, Alfthan H, Stenman UH, Haglund C. Tissue expression of human chorionic gonadotropin beta predicts outcome in colorectal cancer: a comparison with serum expression. Int J Cancer. 2001;95:18–22.

    Article  CAS  PubMed  Google Scholar 

  39. Yamaguchi A, Ishida T, Nishimura G, et al. Human chorionic gonadotropin in colorectal cancer and its relationship to prognosis. Br J Cancer. 1989;60:382–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fukayama M, Hayashi Y, Koike M. Human chorionic gonadotropin in the rectosigmoid colon. Immunohistochemical study on unbalanced distribution of subunits. Am J Pathol. 1987;127:83–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Acevedo HF, Tong JY, Hartsock RJ. Human chorionic gonadotropin-beta subunit gene expression in cultured human fetal and cancer cells of different types and origins. Cancer. 1995;76:1467–75.

    Article  CAS  PubMed  Google Scholar 

  42. Campo E, Palacin A, Benasco C, Quesada E, Cardesa A. Human chorionic gonadotropin in colorectal carcinoma. An immunohistochemical study. Cancer. 1987;59:1611–6.

    Article  CAS  PubMed  Google Scholar 

  43. Moulton HM, Yoshihara PH, Mason DH, Iversen PL, Triozzi PL. Active specific immunotherapy with a beta-human chorionic gonadotropin peptide vaccine in patients with metastatic colorectal cancer: antibody response is associated with improved survival. Clin Cancer Res. 2002;8:2044–51.

    CAS  PubMed  Google Scholar 

  44. Iversen P, Yoshihara P, Moulton H, et al. Active beta-hCG specific immunotherapy in patients with advanced pancreatic cancer. Proc Am Soc Clin Oncol. 2002;23:Abstract #96.

    Google Scholar 

  45. Shin S, Sung BJ, Cho YS, et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry. 2001;40:1117–23.

    Article  CAS  PubMed  Google Scholar 

  46. Mirza A, McGuirk M, Hockenberry TN, et al. Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway. Oncogene. 2002;21:2613–22.

    Article  CAS  PubMed  Google Scholar 

  47. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–21.

    Article  CAS  PubMed  Google Scholar 

  48. Chen X, Duan N, Zhang C, Zhang W. Survivin and tumorigenesis: molecular mechanisms and therapeutic strategies. J Cancer. 2016;7:314–23.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Hirohashi Y, Torigoe T, Maeda A, et al. An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survivin. Clin Cancer Res. 2002;8:1731–9.

    CAS  PubMed  Google Scholar 

  50. Tsuruma T, Hata F, Torigoe T, et al. Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer. J Transl Med. 2004;2:19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Kameshima H, Tsuruma T, Torigoe T, et al. Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients. Cancer Sci. 2011;102:1181–7.

    Article  CAS  PubMed  Google Scholar 

  52. Kameshima H, Tsuruma T, Kutomi G, et al. Immunotherapeutic benefit of alpha-interferon (IFNalpha) in survivin2B-derived peptide vaccination for advanced pancreatic cancer patients. Cancer Sci. 2013;104:124–9.

    Article  CAS  PubMed  Google Scholar 

  53. Lennerz V, Gross S, Gallerani E, et al. Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors. Cancer Immunol Immunother. 2014;63:381–94.

    Article  CAS  PubMed  Google Scholar 

  54. Watson SA, Michaeli D, Grimes S, et al. Gastrimmune raises antibodies that neutralize amidated and glycine-extended gastrin-17 and inhibit the growth of colon cancer. Cancer Res. 1996;56:880–5.

    CAS  PubMed  Google Scholar 

  55. Thorburn CM, Friedman GD, Dickinson CJ, Vogelman JH, Orentreich N, Parsonnet J. Gastrin and colorectal cancer: a prospective study. Gastroenterology. 1998;115:275–80.

    Article  CAS  PubMed  Google Scholar 

  56. Smith JP, Fantaskey AP, Liu G, Zagon IS. Identification of gastrin as a growth peptide in human pancreatic cancer. Am J Physiol. 1995;268:R135–41.

    CAS  PubMed  Google Scholar 

  57. Smith JP, Shih A, Wu Y, McLaughlin PJ, Zagon IS. Gastrin regulates growth of human pancreatic cancer in a tonic and autocrine fashion. Am J Physiol. 1996;270:R1078–84.

    CAS  PubMed  Google Scholar 

  58. Brett BT, Smith SC, Bouvier CV, et al. Phase II study of anti-gastrin-17 antibodies, raised to G17DT, in advanced pancreatic cancer. J Clin Oncol. 2002;20:4225–31.

    Article  CAS  PubMed  Google Scholar 

  59. Gilliam AD, Watson SA, Henwood M, et al. A phase II study of G17DT in gastric carcinoma. Eur J Surg Oncol. 2004;30:536–43.

    Article  CAS  PubMed  Google Scholar 

  60. Ajani JA, Hecht JR, Ho L, et al. An open-label, multinational, multicenter study of G17DT vaccination combined with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or gastroesophageal cancer: the GC4 study. Cancer. 2006;106:1908–16.

    Article  CAS  PubMed  Google Scholar 

  61. Gilliam AD, Broome P, Topuzov EG, et al. An international multicenter randomized controlled trial of G17DT in patients with pancreatic cancer. Pancreas. 2012;41:374–9.

    Article  CAS  PubMed  Google Scholar 

  62. Rocha-Lima CM, de Queiroz Marques Junior E, Bayraktar S, et al. A multicenter phase II study of G17DT immunogen plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan. Cancer Chemother Pharmacol. 2014;74:479–86.

    Article  CAS  PubMed  Google Scholar 

  63. Durrant LG, Buckley DJ, Robins RA, Spendlove I. 105Ad7 cancer vaccine stimulates anti-tumour helper and cytotoxic T-cell responses in colorectal cancer patients but repeated immunisations are required to maintain these responses. Int J Cancer. 2000;85:87–92.

    Article  CAS  PubMed  Google Scholar 

  64. Spendlove I, Li L, Carmichael J, Durrant LG. Decay accelerating factor (CD55): a target for cancer vaccines? Cancer Res. 1999;59:2282–6.

    CAS  PubMed  Google Scholar 

  65. Maxwell-Armstrong CA, Durrant LG, Robins RA, Galvin AM, Scholefield JH, Hardcastle JD. Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105 AD7. Gut. 1999;45:593–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Durrant LG, Maxwell-Armstrong C, Buckley D, et al. A neoadjuvant clinical trial in colorectal cancer patients of the human anti-idiotypic antibody 105 AD7, which mimics CD55. Clin Cancer Res. 2000;6:422–30.

    CAS  PubMed  Google Scholar 

  67. Maxwell-Armstrong CA, Durrant LG, Buckley TJ, et al. Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105 AD7 against placebo in advanced colorectal cancer. Br J Cancer. 2001;84:1443–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ullenhag GJ, Spendlove I, Watson NF, et al. A neoadjuvant/adjuvant randomized trial of colorectal cancer patients vaccinated with an anti-idiotypic antibody, 105 AD7, mimicking CD55. Clin Cancer Res. 2006;12:7389–96.

    Article  CAS  PubMed  Google Scholar 

  69. Staib L, Birebent B, Somasundaram R, et al. Immunogenicity of recombinant GA733-2E antigen (CO17-1A, EGP, KS1-4, KSA, Ep-CAM) in gastro-intestinal carcinoma patients. Int J Cancer. 2001;92:79–87.

    Article  CAS  PubMed  Google Scholar 

  70. Paul AR, Engstrom PF, Weiner LM, Steplewski Z, Koprowski H. Treatment of advanced measurable or evaluable pancreatic carcinoma with 17-1A murine monoclonal antibody alone or in combination with 5-fluorouracil, adriamycin and mitomycin (FAM). Hybridoma. 1986;5 Suppl 1:S171–4.

    PubMed  Google Scholar 

  71. Verrill H, Goldberg M, Rosenbaum R, et al. Clinical trial of Wistar Institute 17-1A monoclonal antibody in patients with advanced gastrointestinal adenocarcinoma: a preliminary report. Hybridoma. 1986;5 Suppl 1:S175–83.

    PubMed  Google Scholar 

  72. Saleh MN, LoBuglio AF, Wheeler RH, et al. A phase II trial of murine monoclonal antibody 17-1A and interferon-gamma: clinical and immunological data. Cancer Immunol Immunother. 1990;32:185–90.

    Article  CAS  PubMed  Google Scholar 

  73. Tempero MA, Sivinski C, Steplewski Z, Harvey E, Klassen L, Kay HD. Phase II trial of interferon gamma and monoclonal antibody 17-1A in pancreatic cancer: biologic and clinical effects. J Clin Oncol. 1990;8:2019–26.

    CAS  PubMed  Google Scholar 

  74. Weiner LM, Harvey E, Padavic-Shaller K, et al. Phase II multicenter evaluation of prolonged murine monoclonal antibody 17-1A therapy in pancreatic carcinoma. J Immunother Emphasis Tumor Immunol. 1993;13:110–6.

    Article  CAS  PubMed  Google Scholar 

  75. Riethmuller G, Schneider-Gadicke E, Schlimok G, et al. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes’ C colorectal carcinoma. German Cancer Aid 17-1A Study Group. Lancet. 1994;343:1177–83.

    Article  CAS  PubMed  Google Scholar 

  76. Riethmuller G, Holz E, Schlimok G, et al. Monoclonal antibody therapy for resected Dukes’ C colorectal cancer: seven-year outcome of a multicenter randomized trial. J Clin Oncol. 1998;16:1788–94.

    CAS  PubMed  Google Scholar 

  77. Ragnhammar P, Fagerberg J, Frodin JE, et al. Effect of monoclonal antibody 17-1A and GM-CSF in patients with advanced colorectal carcinoma – long-lasting, complete remissions can be induced. Int J Cancer. 1993;53:751–8.

    Article  CAS  PubMed  Google Scholar 

  78. Hjelm Skog A, Ragnhammar P, Fagerberg J, et al. Clinical effects of monoclonal antibody 17-1A combined with granulocyte/macrophage-colony-stimulating factor and interleukin-2 for treatment of patients with advanced colorectal carcinoma. Cancer Immunol Immunother. 1999;48:463–70.

    Article  CAS  PubMed  Google Scholar 

  79. Hartung G, Hofheinz RD, Dencausse Y, et al. Adjuvant therapy with edrecolomab versus observation in stage II colon cancer: a multicenter randomized phase III study. Onkologie. 2005;28:347–50.

    CAS  PubMed  Google Scholar 

  80. Punt CJ, Nagy A, Douillard JY, et al. Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study. Lancet. 2002;360:671–7.

    Article  CAS  PubMed  Google Scholar 

  81. Vasef MA, Ross JS, Cohen MB. Telomerase activity in human solid tumors. Diagnostic utility and clinical applications. Am J Clin Pathol. 1999;112:S68–75.

    CAS  PubMed  Google Scholar 

  82. Bernhardt SL, Gjertsen MK, Trachsel S, et al. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II study. Br J Cancer. 2006;95:1474–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Greten TF, Forner A, Korangy F, et al. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma. BMC Cancer. 2010;10:209.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. 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;15:829–40.

    Article  CAS  PubMed  Google Scholar 

  85. 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;37:105–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kaida M, Morita-Hoshi Y, Soeda A, et al. Phase 1 trial of Wilms tumor 1 (WT1) peptide vaccine and gemcitabine combination therapy in patients with advanced pancreatic or biliary tract cancer. J Immunother. 2011;34:92–9.

    Article  CAS  PubMed  Google Scholar 

  87. Staff C, Mozaffari F, Haller BK, Wahren B, Liljefors M. A Phase I safety study of plasmid DNA immunization targeting carcinoembryonic antigen in colorectal cancer patients. Vaccine. 2011;29:6817–22.

    Article  CAS  PubMed  Google Scholar 

  88. Conry RM, Curiel DT, Strong TV, et al. Safety and immunogenicity of a DNA vaccine encoding carcinoembryonic antigen and hepatitis B surface antigen in colorectal carcinoma patients. Clin Cancer Res. 2002;8:2782–7.

    CAS  PubMed  Google Scholar 

  89. Wang J, Reiss KA, Khatri R, Jaffee E, Laheru D. Immune therapy in GI malignancies: a review. J Clin Oncol. 2015;33:1745–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Pastan I, Hassan R. Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res. 2014;74:2907–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. 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;19:145–56.

    CAS  PubMed  Google Scholar 

  92. 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;253:328–35.

    Article  PubMed  PubMed Central  Google Scholar 

  93. 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;14:1455–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. 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;33:1325–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. 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;36:382–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Le DT, Crocenzi TS, Uram JN, et al. Randomized phase 2 study of the safety, efficacy, and immune response of GVAX pancreas (with cyclophosphamide) and CRS-207 with or without nivolumab in patients with previously treated metastatic pancreatic adenocarcinoma (STELLAR). J Clin Oncol. 2016;34:abstr TPS4153.

    Google Scholar 

  97. Uyl-de Groot CA, Vermorken JB, Hanna Jr MG, et al. Immunotherapy with autologous tumor cell-BCG vaccine in patients with colon cancer: a prospective study of medical and economic benefits. Vaccine. 2005;23:2379–87.

    Article  CAS  PubMed  Google Scholar 

  98. Hardacre JM, Mulcahy M, Small W, et al. Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: a phase 2 study. J Gastrointest Surg. 2013;17:94–100; discussion p -1.

    Article  PubMed  Google Scholar 

  99. Joziasse DH, Oriol R. Xenotransplantation: the importance of the Galalpha1,3Gal epitope in hyperacute vascular rejection. Biochim Biophys Acta. 1999;1455:403–18.

    Article  CAS  PubMed  Google Scholar 

  100. Baumann BC, Forte P, Hawley RJ, Rieben R, Schneider MK, Seebach JD. Lack of galactose-alpha-1,3-galactose expression on porcine endothelial cells prevents complement-induced lysis but not direct xenogeneic NK cytotoxicity. J Immunol. 2004;172:6460–7.

    Article  CAS  PubMed  Google Scholar 

  101. Schaapherder AF, Daha MR, te Bulte MT, van der Woude FJ, Gooszen HG. Antibody-dependent cell-mediated cytotoxicity against porcine endothelium induced by a majority of human sera. Transplantation. 1994;57:1376–82.

    Article  CAS  PubMed  Google Scholar 

  102. Watier H, Guillaumin JM, Vallee I, et al. Human NK cell-mediated direct and IgG-dependent cytotoxicity against xenogeneic porcine endothelial cells. Transpl Immunol. 1996;4:293–9.

    Article  CAS  PubMed  Google Scholar 

  103. Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008;299:1019–26.

    Article  CAS  PubMed  Google Scholar 

  104. Remondo C, Cereda V, Mostbock S, et al. Human dendritic cell maturation and activation by a heat-killed recombinant yeast (Saccharomyces cerevisiae) vector encoding carcinoembryonic antigen. Vaccine. 2009;27:987–94.

    Article  CAS  PubMed  Google Scholar 

  105. King TH, Kemmler CB, Guo Z, et al. A whole recombinant yeast-based therapeutic vaccine elicits HBV X, S and Core specific T cells in mice and activates human T cells recognizing epitopes linked to viral clearance. PLoS One. 2014;9:e101904.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Wansley EK, Chakraborty M, Hance KW, et al. Vaccination with a recombinant Saccharomyces cerevisiae expressing a tumor antigen breaks immune tolerance and elicits therapeutic antitumor responses. Clin Cancer Res. 2008;14:4316–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Gaggar A, Coeshott C, Apelian D, et al. Safety, tolerability and immunogenicity of GS-4774, a hepatitis B virus-specific therapeutic vaccine, in healthy subjects: a randomized study. Vaccine. 2014;32:4925–31.

    Article  CAS  PubMed  Google Scholar 

  108. Bilusic M, Heery CR, Arlen PM, et al. Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma. Cancer Immunol Immunother. 2014;63:225–34.

    Article  CAS  PubMed  Google Scholar 

  109. Chaft JE, Litvak A, Arcila ME, et al. Phase II study of the GI-4000 KRAS vaccine after curative therapy in patients with stage I-III lung adenocarcinoma harboring a KRAS G12C, G12D, or G12V mutation. Clin Lung Cancer. 2014;15:405–10.

    Article  CAS  PubMed  Google Scholar 

  110. Roselli M, Fernando RI, Guadagni F, et al. Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in human lung tumors: an opportunity for novel interventions against lung cancer. Clin Cancer Res. 2012;18:3868–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Hamilton DH, Litzinger MT, Jales A, et al. Immunological targeting of tumor cells undergoing an epithelial-mesenchymal transition via a recombinant brachyury-yeast vaccine. Oncotarget. 2013;4:1777–90.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Fernando RI, Litzinger M, Trono P, Hamilton DH, Schlom J, Palena C. The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells. J Clin Invest. 2010;120:533–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Heery CR, Singh BH, Rauckhorst M, et al. Phase I trial of a yeast-based therapeutic cancer vaccine (GI-6301) targeting the transcription factor brachyury. Cancer Immunol Res. 2015;3:1248–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Schlom J. Therapeutic cancer vaccines: current status and moving forward. J Natl Cancer Inst. 2012;104:599–613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Kim JW, Gulley JL. Poxviral vectors for cancer immunotherapy. Expert Opin Biol Ther. 2012;12:463–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Hodge JW, McLaughlin JP, Kantor JA, Schlom J. Diversified prime and boost protocols using recombinant vaccinia virus and recombinant non-replicating avian pox virus to enhance T-cell immunity and antitumor responses. Vaccine. 1997;15:759–68.

    Article  CAS  PubMed  Google Scholar 

  117. Marshall JL, Hoyer RJ, Toomey MA, et al. Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses. J Clin Oncol. 2000;18:3964–73.

    CAS  PubMed  Google Scholar 

  118. Hodge JW, Higgins J, Schlom J. Harnessing the unique local immunostimulatory properties of modified vaccinia Ankara (MVA) virus to generate superior tumor-specific immune responses and antitumor activity in a diversified prime and boost vaccine regimen. Vaccine. 2009;27:4475–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Schlom J, Sabzevari H, Grosenbach DW, Hodge JW. A triad of costimulatory molecules synergize to amplify T-cell activation in both vector-based and vector-infected dendritic cell vaccines. Artif Cells Blood Substit Immobil Biotechnol. 2003;31:193–228.

    Article  CAS  PubMed  Google Scholar 

  120. Hodge JW, Sabzevari H, Yafal AG, Gritz L, Lorenz MG, Schlom J. A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res. 1999;59:5800–7.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  122. Heery CR, Ibrahim NK, Arlen PM, et al. Docetaxel alone or in combination with a therapeutic cancer vaccine (PANVAC) in patients with metastatic breast cancer: a randomized clinical trial. JAMA Oncol. 2015;1:1087–95.

    Article  PubMed  Google Scholar 

  123. 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;23:720–31.

    Article  CAS  PubMed  Google Scholar 

  124. Sarkar D, Shields B, Davies ML, Muller J, Wakeman JA. BRACHYURY confers cancer stem cell characteristics on colorectal cancer cells. Int J Cancer. 2012;130:328–37.

    Article  CAS  PubMed  Google Scholar 

  125. Kilic N, Feldhaus S, Kilic E, et al. Brachyury expression predicts poor prognosis at early stages of colorectal cancer. Eur J Cancer. 2011;47:1080–5.

    Article  PubMed  Google Scholar 

  126. Du R, Wu S, Lv X, Fang H, Wu S, Kang J. Overexpression of brachyury contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma. J Exp Clin Cancer Res. 2014;33:105.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Heery CR, Donahue RN, Lepone L, et al. Phase I, dose-escalation, clinical trial of MVA-Brachyury-TRICOM vaccine demonstrating safety and brachyury-specific T cell responses. 30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015); Maryland: National Harbor; 2015. p. 132.

    Google Scholar 

  128. Amalfitano A, Hauser MA, Hu H, Serra D, Begy CR, Chamberlain JS. Production and characterization of improved adenovirus vectors with the E1, E2b, and E3 genes deleted. J Virol. 1998;72:926–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Gabitzsch ES, Xu Y, Yoshida LH, Balint J, Amalfitano A, Jones FR. Novel Adenovirus type 5 vaccine platform induces cellular immunity against HIV-1 Gag, Pol, Nef despite the presence of Ad5 immunity. Vaccine. 2009;27:6394–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Gabitzsch ES, Xu Y, Balint Jr JP, Hartman ZC, Lyerly HK, Jones FR. Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA. Cancer Immunol Immunother. 2010;59:1131–5.

    Article  CAS  PubMed  Google Scholar 

  131. Morse MA, Chaudhry A, Gabitzsch ES, et al. Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients. Cancer Immunol Immunother. 2013;62:1293–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Morse MA, Clay TM, Hobeika AC, et al. Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules. Clin Cancer Res. 2005;11:3017–24.

    Article  CAS  PubMed  Google Scholar 

  133. Morse MA, Deng Y, Coleman D, et al. A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin Cancer Res. 1999;5:1331–8.

    CAS  PubMed  Google Scholar 

  134. Morse MA, Niedzwiecki D, Marshall JL, et al. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer. Ann Surg. 2013;258:879–86.

    Article  PubMed  Google Scholar 

  135. Trinchieri G. Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol. 2012;30:677–706.

    Article  CAS  PubMed  Google Scholar 

  136. Triantafillidis JK, Nasioulas G, Kosmidis PA. Colorectal cancer and inflammatory bowel disease: epidemiology, risk factors, mechanisms of carcinogenesis and prevention strategies. Anticancer Res. 2009;29:2727–37.

    PubMed  Google Scholar 

  137. Multhoff G, Molls M, Radons J. Chronic inflammation in cancer development. Front Immunol. 2011;2:98.

    PubMed  Google Scholar 

  138. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14:1014–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Janeway Jr CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216.

    Article  CAS  PubMed  Google Scholar 

  140. Piccinini AM, Midwood KS. DAMPening inflammation by modulating TLR signalling. Mediators Inflamm 2010;2010.

    Google Scholar 

  141. Ludgate CM. Optimizing cancer treatments to induce an acute immune response: radiation Abscopal effects, PAMPs, and DAMPs. Clin Cancer Res. 2012;18:4522–5.

    Article  CAS  PubMed  Google Scholar 

  142. Chow MT, Moller A, Smyth MJ. Inflammation and immune surveillance in cancer. Semin Cancer Biol. 2012;22:23–32.

    Article  CAS  PubMed  Google Scholar 

  143. Escamilla-Tilch M, Filio-Rodriguez G, Garcia-Rocha R, et al. The interplay between pathogen-associated and danger-associated molecular patterns: an inflammatory code in cancer? Immunol Cell Biol. 2013;91:601–10.

    Article  CAS  PubMed  Google Scholar 

  144. Juncadella IJ, Kadl A, Sharma AK, et al. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature. 2013;493:547–51.

    Article  CAS  PubMed  Google Scholar 

  145. Fadok VA, Chimini G. The phagocytosis of apoptotic cells. Semin Immunol. 2001;13:365–72.

    Article  CAS  PubMed  Google Scholar 

  146. Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol. 2005;6:1191–7.

    Article  CAS  PubMed  Google Scholar 

  147. Zelenay S, Reis e Sousa C. Adaptive immunity after cell death. Trends Immunol. 2013;34:329–35.

    Article  CAS  PubMed  Google Scholar 

  148. Drexler SK, Foxwell BM. The role of toll-like receptors in chronic inflammation. Int J Biochem Cell Biol. 2010;42:506–18.

    Article  CAS  PubMed  Google Scholar 

  149. Marshak-Rothstein A, Rifkin IR. Immunologically active autoantigens: the role of toll-like receptors in the development of chronic inflammatory disease. Annu Rev Immunol. 2007;25:419–41.

    Article  CAS  PubMed  Google Scholar 

  150. Uhl M, Kepp O, Jusforgues-Saklani H, Vicencio JM, Kroemer G, Albert ML. Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cells. Cell Death Differ. 2009;16:991–1005.

    Article  CAS  PubMed  Google Scholar 

  151. Rovere-Querini P, Capobianco A, Scaffidi P, et al. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep. 2004;5:825–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Rawson PM, Molette C, Videtta M, et al. Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection. Nat Med. 2007;13:1431–9.

    Article  CAS  PubMed  Google Scholar 

  153. Woo SR, Corrales L, Gajewski TF. Innate immune recognition of cancer. Annu Rev Immunol. 2015;33:445–74.

    Article  CAS  PubMed  Google Scholar 

  154. Dudek AM, Garg AD, Krysko DV, De Ruysscher D, Agostinis P. Inducers of immunogenic cancer cell death. Cytokine Growth Factor Rev. 2013;24:319–33.

    Article  CAS  PubMed  Google Scholar 

  155. Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012;12:860–75.

    Article  CAS  PubMed  Google Scholar 

  156. Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16:375–84.

    Article  CAS  PubMed  Google Scholar 

  157. Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32:1020–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.

    Article  CAS  PubMed  Google Scholar 

  159. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Zdanov S, Mandapathil M, Abu Eid R, et al. Mutant KRAS conversion of conventional T cells into regulatory T cells. Cancer Immunol Res. 2016;4:354–65.

    Article  CAS  PubMed  Google Scholar 

  163. 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;19:6286–95.

    Article  CAS  PubMed  Google Scholar 

  164. 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;149:201–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Winograd R, Byrne KT, Evans RA, et al. Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma. Cancer Immunol Res. 2015;3:399–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Hodge JW, Garnett CT, Farsaci B, et al. Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death. Int J Cancer. 2013;133:624–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Hodge JW, Kwilas A, Ardiani A, Gameiro SR. Attacking malignant cells that survive therapy: exploiting immunogenic modulation. Oncoimmunology. 2013;2:e26937.

    Article  PubMed  PubMed Central  Google Scholar 

  168. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72.

    Article  CAS  PubMed  Google Scholar 

  169. Zitvogel L, Kepp O, Senovilla L, Menger L, Chaput N, Kroemer G. Immunogenic tumor cell death for optimal anticancer therapy: the calreticulin exposure pathway. Clin Cancer Res. 2010;16:3100–4.

    Article  CAS  PubMed  Google Scholar 

  170. Hodge JW, Ardiani A, Farsaci B, Kwilas AR, Gameiro SR. The tipping point for combination therapy: cancer vaccines with radiation, chemotherapy, or targeted small molecule inhibitors. Semin Oncol. 2012;39:323–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Weden S, Klemp M, Gladhaug IP, et al. Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. Int J Cancer. 2011;128:1120–8.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD, USA

    Chris Heery

  2. Ruesch Center for the Cure of GI Cancers, Georgetown University, Lombardi Comprehensive Cancer Center, 3800 Reservoir RD NW, Washington, DC, 20007, USA

    Anteneh Tesfaye, Benjamin Weinberg & John Marshall

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  1. Chris Heery
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  2. Anteneh Tesfaye
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  4. John Marshall
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  1. Nuffield Division of Clinical and Laboratory Sciences, University of Oxford, Oxford, United Kingdom

    David Kerr

  2. John Radcliffe Hospital, Oxford University Hospitals NHS Trust John Radcliffe Hospital, Oxfordshire, United Kingdom

    Rebecca Johnson

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Heery, C., Tesfaye, A., Weinberg, B., Marshall, J. (2017). Therapeutic Cancer Vaccines. In: Kerr, D., Johnson, R. (eds) Immunotherapy for Gastrointestinal Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-43063-8_3

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