Skip to main content

Advertisement

Log in

Current status of vaccine immunotherapy for gastrointestinal cancers

  • Review Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Recent advances in tumor immunology and molecular drug development have ushered in a new era of cancer immunotherapy. Immunotherapy has shown promising results for several types of tumors, such as advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin’s lymphoma. Similarly, efforts have been made to develop immunotherapies such as adoptive T-cell transplantation, peptide vaccines, and dendritic cell vaccines, specifically for gastrointestinal tumors. However, before the advent of immune checkpoint inhibitors, immunotherapy did not work as well as expected. In this article, we review immunotherapy, focusing on cancer vaccines for gastrointestinal tumors, which generally target eliciting tumor-specific CD8 + cytotoxic T lymphocytes (CTLs). We also review various vaccine therapies and describe the relationship between vaccines and adjuvants. Finally, we discuss prospects for the combination of immunotherapy with immune checkpoint inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  2. Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, et al. Randomized phase III KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J Clin Oncol. 2020;38:4138–48.

    Article  CAS  PubMed  Google Scholar 

  3. Kato K, Cho BC, Takahashi M, Okada M, Lin CY, Chin K, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:1506–17.

    Article  CAS  PubMed  Google Scholar 

  4. Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71.

    Article  CAS  PubMed  Google Scholar 

  5. Le DT, Kim TW, Van Cutsem E, Geva R, Jäger D, Hara H, et al. Phase II open-label study of pembrolizumab in treatment-refractory, microsatellite instability–high/mismatch repair–deficient metastatic colorectal cancer: KEYNOTE-164. J Clin Oncol. 2020;38:11.

    Article  CAS  PubMed  Google Scholar 

  6. Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022; 1:EVIDoa2100070.

  7. Boku N, Ryu MH, Kato K, Chung HC, Minashi K, Lee KW, et al. Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4). Ann Oncol. 2019;30:250–8.

    Article  CAS  PubMed  Google Scholar 

  8. Sun J-M, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, et al: Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. The Lancet. 2021; 398:759–771.

  9. André T, Shiu K-K, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab in microsatellite-instability–high advanced colorectal cancer. N Engl J Med. 2020;383:2207–18.

    Article  PubMed  Google Scholar 

  10. Wang J, Xiu J, Farrell A, Baca Y, Arai H, Battaglin F, et al. Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study. Lancet Oncol. 2023;24:151–61.

    Article  PubMed  PubMed Central  Google Scholar 

  11. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991;254:1643–7.

    Article  PubMed  Google Scholar 

  12. Melssen M, Slingluff CL Jr. Vaccines targeting helper T cells for cancer immunotherapy. Curr Opin Immunol. 2017;47:85–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Toes RE, Offringa R, Blom RJ, Melief CJ, Kast WM. Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction. Proc Natl Acad Sci USA. 1996;93:7855–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hazama S, Nakamura Y, Takenouchi H, Suzuki N, Tsunedomi R, Inoue Y, et al. A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome. J Transl Med. 2014;12:63.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hazama S, Nakamura Y, Tanaka H, Hirakawa K, Tahara K, Shimizu R, et al. A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study). J Transl Med. 2014;12:108.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hazama S, Takenouchi H, Tsunedomi R, Iida M, Suzuki N, Iizuka N, et al. Predictive biomarkers for the outcome of vaccination of five therapeutic epitope peptides for colorectal cancer. Anticancer Res. 2014;34:4201–5.

    CAS  PubMed  Google Scholar 

  17. Shindo Y, Hazama S, Suzuki N, Iguchi H, Uesugi K, Tanaka H, et al. Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer. J Exp Clin Cancer Res. 2017;36:36.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kano Y, Iguchi T, Matsui H, Adachi K, Sakoda Y, Miyakawa T, et al. Combined adjuvants of poly(I:C) plus LAG-3-Ig improve antitumor effects of tumor-specific T cells, preventing their exhaustion. Cancer Sci. 2016;107:398–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Benwell RK, Hruska JE, Fritsche KL, Lee DR. Double stranded RNA- relative to other TLR ligand-activated dendritic cells induce extremely polarized human Th1 responses. Cell Immunol. 2010;264:119–26.

    Article  CAS  PubMed  Google Scholar 

  20. Verdijk RM, Mutis T, Esendam B, Kamp J, Melief CJ, Brand A, et al. Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells. J Immunol. 1999;163:57–61.

    Article  CAS  PubMed  Google Scholar 

  21. Andreae S, Piras F, Burdin N, Triebel F. Maturation and activation of dendritic cells induced by lymphocyte activation gene-3 (CD223). J Immunol. 2002;168:3874–80.

    Article  CAS  PubMed  Google Scholar 

  22. Avice MN, Sarfati M, Triebel F, Delespesse G, Demeure CE. Lymphocyte activation gene-3, a MHC class II ligand expressed on activated T cells, stimulates TNF-alpha and IL-12 production by monocytes and dendritic cells. J Immunol. 1999;162:2748–53.

    Article  CAS  PubMed  Google Scholar 

  23. Maeda TK, Sugiura D, Okazaki IM, Maruhashi T, Okazaki T. Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation. J Biol Chem. 2019;294:6017–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Matsui H, Hazama S, Tamada K, Udaka K, Irie A, Nishimura Y, et al. Identification of a promiscuous epitope peptide derived From HSP70. J Immunother. 2019;42:244–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nakajima M, Hazama S, Tamada K, Udaka K, Kouki Y, Uematsu T, et al. A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial. Cancer Immunol Immunother. 2020;69:1651–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nakajima M, Hazama S, Tokumitsu Y, Shindo Y, Matsui H, Matsukuma S, et al. A phase I study of a novel therapeutic vaccine as perioperative treatment for patients with surgically resectable hepatocellular carcinoma: The YCP02 trial. Hepatol Res 2023.

  27. Kurebayashi Y, Ojima H, Tsujikawa H, Kubota N, Maehara J, Abe Y, et al. Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification. Hepatology. 2018;68:1025–41.

    Article  CAS  PubMed  Google Scholar 

  28. Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind. Phase III Trial. J Clin Oncol. 2020;38:193–202.

    Article  CAS  PubMed  Google Scholar 

  29. Harding JJ, Nandakumar S, Armenia J, Khalil DN, Albano M, Ly M, et al. Prospective genotyping of hepatocellular carcinoma: clinical implications of next-generation sequencing for matching patients to targeted and immune therapies. Clin Cancer Res. 2019;25:2116–26.

    Article  CAS  PubMed  Google Scholar 

  30. Bujas T, Marusic Z, Peric Balja M, Mijic A, Kruslin B, Tomas D. MAGE-A3/4 and NY-ESO-1 antigens expression in metastatic esophageal squamous cell carcinoma. Eur J Histochem. 2011;55: e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Iinuma H, Fukushima R, Inaba T, Tamura J, Inoue T, Ogawa E, et al. Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients. J Transl Med. 2014;12:84.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kono K, Iinuma H, Akutsu Y, Tanaka H, Hayashi N, Uchikado Y, et al. Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens. J Transl Med. 2012;10:141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Murahashi M, Hijikata Y, Yamada K, Tanaka Y, Kishimoto J, Inoue H, et al. Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors. Clin Immunol. 2016;166–167:48–58.

    Article  PubMed  Google Scholar 

  34. Hoos A, Levey DL. Vaccination with heat shock protein-peptide complexes: from basic science to clinical applications. Expert Rev Vaccin. 2003;2:369–79.

    Article  CAS  Google Scholar 

  35. Zhang W, Lu X, Cui P, Piao C, Xiao M, Liu X, et al. Phase I/II clinical trial of a Wilms’ tumor 1-targeted dendritic cell vaccination-based immunotherapy in patients with advanced cancer. Cancer Immunol Immunother. 2019;68:121–30.

    Article  CAS  PubMed  Google Scholar 

  36. Masuzawa T, Fujiwara Y, Okada K, Nakamura A, Takiguchi S, Nakajima K, et al. Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer. Int J Oncol. 2012;41:1297–304.

    Article  CAS  PubMed  Google Scholar 

  37. Sato Y, Fujiwara T, Mine T, Shomura H, Homma S, Maeda Y, et al. Immunological evaluation of personalized peptide vaccination in combination with a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma patients. Cancer Sci. 2007;98:1113–9.

    Article  CAS  PubMed  Google Scholar 

  38. Kawamura J, Sugiura F, Sukegawa Y, Yoshioka Y, Hida JI, Hazama S, et al. Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stage III colorectal cancer. Oncol Lett. 2018;15:4241–7.

    PubMed  PubMed Central  Google Scholar 

  39. Kameshima H, Tsuruma T, Torigoe T, Takahashi A, Hirohashi Y, Tamura Y, 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 

  40. Kloor M, Reuschenbach M, Pauligk C, Karbach J, Rafiyan MR, Al-Batran SE, et al. A frameshift peptide neoantigen-based vaccine for mismatch repair-deficient cancers: a phase I/IIa clinical trial. Clin Cancer Res. 2020;26:4503–10.

    Article  CAS  PubMed  Google Scholar 

  41. Katsuda M, Miyazawa M, Ojima T, Katanuma A, Hakamada K, Sudo K, et al. A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy. Trials. 2019;20:242.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Suzuki N, Hazama S, Iguchi H, Uesugi K, Tanaka H, Hirakawa K, et al. Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study. Cancer Sci. 2017;108:73–80.

    Article  CAS  PubMed  Google Scholar 

  43. Suzuki N, Hazama S, Ueno T, Matsui H, Shindo Y, Iida M, et al. A phase I clinical trial of vaccination with KIF20A-derived peptide in combination with gemcitabine for patients with advanced pancreatic cancer. J Immunother. 2014;37:36–42.

    Article  CAS  PubMed  Google Scholar 

  44. Miyazawa M, Katsuda M, Maguchi H, Katanuma A, Ishii H, Ozaka M, et al. Phase II clinical trial using novel peptide cocktail vaccine as a postoperative adjuvant treatment for surgically resected pancreatic cancer patients. Int J Cancer. 2017;140:973–82.

    Article  CAS  PubMed  Google Scholar 

  45. Yamaue H, Tsunoda T, Tani M, Miyazawa M, Yamao K, Mizuno N, et al. Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC study. Cancer Sci. 2015;106:883–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Middleton G, Silcocks P, Cox T, Valle J, Wadsley J, Propper D, 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 

  47. Yanagisawa R, Koizumi T, Koya T, Sano K, Koido S, Nagai K, et al. WT1-pulsed dendritic cell vaccine combined with chemotherapy for resected pancreatic cancer in a phase I study. Anticancer Res. 2018;38:2217–25.

    CAS  PubMed  Google Scholar 

  48. Löffler MW, Gori S, Izzo F, Mayer-Mokler A, Ascierto PA, Königsrainer A, et al. Phase I/II multicenter trial of a novel therapeutic cancer vaccine, HepaVac-101, for hepatocellular carcinoma. Clin Cancer Res. 2022;28:2555–66.

    Article  PubMed  Google Scholar 

  49. Sawada Y, Yoshikawa T, Ofuji K, Yoshimura M, Tsuchiya N, Takahashi M, et al. Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients. Oncoimmunology. 2016;5: e1129483.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sawada Y, Yoshikawa T, Nobuoka D, Shirakawa H, Kuronuma T, Motomura Y, et al. Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival. Clin Cancer Res. 2012;18:3686–96.

    Article  CAS  PubMed  Google Scholar 

  51. Ikeda M, Okusaka T, Ohno I, Mitsunaga S, Kondo S, Ueno H, et al. Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma. Immunotherapy. 2021;13:371–85.

    Article  CAS  PubMed  Google Scholar 

  52. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med. 1973;137:1142–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Shindo Y, Hazama S, Maeda Y, Matsui H, Iida M, Suzuki N, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Yang J, Shangguan J, Eresen A, Li Y, Wang J, Zhang Z. Dendritic cells in pancreatic cancer immunotherapy: vaccines and combination immunotherapies. Pathol Res Pract. 2019;215: 152691.

    Article  CAS  PubMed  Google Scholar 

  55. Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020;20:7–24.

    Article  CAS  PubMed  Google Scholar 

  56. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.

    Article  CAS  PubMed  Google Scholar 

  57. Takashima M, Kuramitsu Y, Yokoyama Y, Iizuka N, Toda T, Sakaida I, et al. Proteomic profiling of heat shock protein 70 family members as biomarkers for hepatitis C virus-related hepatocellular carcinoma. Proteomics. 2003;3:2487–93.

    Article  CAS  PubMed  Google Scholar 

  58. Yoshida S, Hazama S, Tokuno K, Sakamoto K, Takashima M, Tamesa T, et al. Concomitant overexpression of heat-shock protein 70 and HLA class-I in hepatitis C virus-related hepatocellular carcinoma. Anticancer Res. 2009;29:539–44.

    PubMed  Google Scholar 

  59. Maeda Y, Yoshimura K, Matsui H, Shindo Y, Tamesa T, Tokumitsu Y, et al. Dendritic cells transfected with heat-shock protein 70 messenger RNA for patients with hepatitis C virus-related hepatocellular carcinoma: a phase 1 dose escalation clinical trial. Cancer Immunol Immunother. 2015;64:1047–56.

    Article  CAS  PubMed  Google Scholar 

  60. Matsui H, Hazama S, Nakajima M, Xu M, Matsukuma S, Tokumitsu Y, et al. Correction to: Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepatocellular carcinoma: a phase I/II prospective randomized controlled clinical trial. Cancer Immunol Immunother. 2021;70:959.

    Article  PubMed  Google Scholar 

  61. Rastogi I, Muralidhar A, McNeel DG: Vaccines as treatments for prostate cancer. Nat Rev Urol. 2023:1–16.

  62. Madan RA, Antonarakis ES, Drake CG, Fong L, Yu EY, McNeel DG, et al. Putting the pieces together: completing the mechanism of action jigsaw for sipuleucel-T. JNCI J Natl Cancer Inst. 2020;112:562–73.

    Article  PubMed  Google Scholar 

  63. Zhang L, Kandadi H, Yang H, Cham J, He T, Oh DY, et al. Long-term sculpting of the B-cell repertoire following cancer immunotherapy in patients treated with Sipuleucel-T. Cancer Immunol Res. 2020;8:1496–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature. 2001;411:375–9.

    Article  CAS  PubMed  Google Scholar 

  65. Torphy RJ, Zhu Y, Schulick RD. Immunotherapy for pancreatic cancer: barriers and breakthroughs. Ann Gastroenterol Surg. 2018;2:274–81.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Shindo Y, Yoshimura K, Kuramasu A, Watanabe Y, Ito H, Kondo T, et al. Combination immunotherapy with 4–1BB activation and PD-1 blockade enhances antitumor efficacy in a mouse model of subcutaneous tumor. Anticancer Res. 2015;35:129–36.

    CAS  PubMed  Google Scholar 

  67. Santos PM, Adamik J, Howes TR, Du S, Vujanovic L, Warren S, et al. Impact of checkpoint blockade on cancer vaccine-activated CD8+ T cell responses. J Exp Med. 2020;217.

  68. Hassannia H, Ghasemi Chaleshtari M, Atyabi F, Nosouhian M, Masjedi A, Hojjat-Farsangi M, et al. Blockage of immune checkpoint molecules increases T-cell priming potential of dendritic cell vaccine. Immunology. 2020;159:75–87.

    Article  CAS  PubMed  Google Scholar 

  69. Gulla SK, Rao BR, Moku G, Jinka S, Nimmu NV, Khalid S, et al. In vivo targeting of DNA vaccines to dendritic cells using functionalized gold nanoparticles. Biomater Sci. 2019;7:773–88.

    Article  CAS  PubMed  Google Scholar 

  70. Tacken PJ, de Vries IJ, Torensma R, Figdor CG. Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol. 2007;7:790–802.

    Article  CAS  PubMed  Google Scholar 

  71. Affandi AJ, Grabowska J, Olesek K, Lopez Venegas M, Barbaria A, Rodríguez E, et al. Selective tumor antigen vaccine delivery to human CD169(+) antigen-presenting cells using ganglioside-liposomes. Proc Natl Acad Sci USA. 2020;117:27528–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Rice J, Ottensmeier CH, Stevenson FK. DNA vaccines: precision tools for activating effective immunity against cancer. Nat Rev Cancer. 2008;8:108–20.

    Article  CAS  PubMed  Google Scholar 

  73. Liu MA. A comparison of plasmid DNA and mRNA as vaccine technologies. Vaccines (Basel) 2019;7.

  74. Singhal P, Naswa S, Marfatia YS. Pregnancy and sexually transmitted viral infections. Indian J Sex Transm Dis AIDS. 2009;30:71–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Peng S, Ferrall L, Gaillard S, Wang C, Chi WY, Huang CH, et al. Development of DNA vaccine targeting E6 and E7 proteins of human papillomavirus 16 (HPV16) and HPV18 for immunotherapy in combination with recombinant vaccinia boost and PD-1 antibody. mBio 2021;12.

  76. Lopes A, Vandermeulen G, Préat V. Cancer DNA vaccines: current preclinical and clinical developments and future perspectives. J Exp Clin Cancer Res. 2019;38:146.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Kallen KJ, Heidenreich R, Schnee M, Petsch B, Schlake T, Thess A, et al. A novel, disruptive vaccination technology: self-adjuvanted RNActive(®) vaccines. Hum Vaccin Immunother. 2013;9:2263–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Hassett KJ, Benenato KE, Jacquinet E, Lee A, Woods A, Yuzhakov O, et al. Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol Ther Nucl Acids. 2019;15:1–11.

    Article  CAS  Google Scholar 

  79. Wadhwa A, Aljabbari A, Lokras A, Foged C, Thakur A. Opportunities and challenges in the delivery of mRNA-based vaccines. Pharmaceutics. 2020;12.

  80. Miao L, Zhang Y, Huang L. mRNA vaccine for cancer immunotherapy. Mol Cancer. 2021;20:41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015;5:123–7.

    Article  PubMed  Google Scholar 

  82. Persano S, Guevara ML, Li Z, Mai J, Ferrari M, Pompa PP, et al. Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination. Biomaterials. 2017;125:81–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603–15.

    Article  CAS  PubMed  Google Scholar 

  84. Boczkowski D, Nair SK, Snyder D, Gilboa E. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med. 1996;184:465–72.

    Article  CAS  PubMed  Google Scholar 

  85. Huang X, Tang T, Zhang G, Liang T. Identification of tumor antigens and immune subtypes of cholangiocarcinoma for mRNA vaccine development. Mol Cancer. 2021;20:50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Huang X, Zhang G, Tang T, Liang T. Identification of tumor antigens and immune subtypes of pancreatic adenocarcinoma for mRNA vaccine development. Mol Cancer. 2021;20:44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Löwer M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547:222–6.

    Article  CAS  PubMed  Google Scholar 

  88. Cafri G, Gartner JJ, Zaks T, Hopson K, Levin N, Paria BC, et al. mRNA vaccine-induced neoantigen-specific T cell immunity in patients with gastrointestinal cancer. J Clin Invest. 2020;130:5976–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lorentzen CL, Haanen JB, Met Ö, Svane IM. Clinical advances and ongoing trials on mRNA vaccines for cancer treatment. Lancet Oncol. 2022;23:e450–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sahin U, Oehm P, Derhovanessian E, Jabulowsky RA, Vormehr M, Gold M, et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020;585:107–12.

    Article  CAS  PubMed  Google Scholar 

  91. Wysocki PJ, Kazimierczak U, Suchorska W, Kotlarski M, Malicki J, Mackiewicz A. Gene-modified tumor vaccine secreting a designer cytokine Hyper-Interleukin-6 is an effective therapy in mice bearing orthotopic renal cell cancer. Cancer Gene Ther. 2010;17:465–75.

    Article  CAS  PubMed  Google Scholar 

  92. Novak L, Igoucheva O, Cho S, Alexeev V. Characterization of the CCL21-mediated melanoma-specific immune responses and in situ melanoma eradication. Mol Cancer Ther. 2007;6:1755–64.

    Article  CAS  PubMed  Google Scholar 

  93. Dranoff G. GM-CSF-based cancer vaccines. Immunol Rev. 2002;188:147–54.

    Article  CAS  PubMed  Google Scholar 

  94. Vermaelen K. Vaccine strategies to improve anti-cancer cellular immune responses. Front Immunol. 2019;10:8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Habal N, Gupta RK, Bilchik AJ, Yee R, Leopoldo Z, Ye W, et al. CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer. Ann Surg Oncol. 2001;8:389–401.

    Article  CAS  PubMed  Google Scholar 

  96. Uyl-de Groot CA, Vermorken JB, Hanna MG Jr, Verboom P, Groot MT, Bonsel GJ, 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 

  97. Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, 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 

  98. Le DT, Picozzi VJ, Ko AH, Wainberg ZA, Kindler H, Wang-Gillam A, et al. Results from a Phase IIb, randomized, multicenter study of GVAX pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE study). Clin Cancer Res. 2019;25:5493–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Wu AA, Bever KM, Ho WJ, Fertig EJ, Niu N, Zheng L, et al. A phase II study of allogeneic GM-CSF-transfected pancreatic tumor vaccine (GVAX) with ipilimumab as maintenance treatment for metastatic pancreatic cancer. Clin Cancer Res. 2020;26:5129–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Rosenberg SA, Dudley ME. Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes. Proc Natl Acad Sci USA. 2004;101(Suppl 2):14639–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Secrier M, Li X, de Silva N, Eldridge MD, Contino G, Bornschein J, et al. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance. Nat Genet. 2016;48:1131–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Gao YB, Chen ZL, Li JG, Hu XD, Shi XJ, Sun ZM, et al. Genetic landscape of esophageal squamous cell carcinoma. Nat Genet. 2014;46:1097–102.

    Article  CAS  PubMed  Google Scholar 

  103. Liu Q, Chu Y, Shao J, Qian H, Yang J, Sha H, et al. Benefits of an immunogenic personalized neoantigen nanovaccine in patients with high-risk gastric/gastroesophageal junction cancer. Adv Sci (Weinh). 2022;10: e2203298.

    Article  PubMed  Google Scholar 

  104. van den Bulk J, Verdegaal EME, Ruano D, Ijsselsteijn ME, Visser M, van der Breggen R, et al. Neoantigen-specific immunity in low mutation burden colorectal cancers of the consensus molecular subtype 4. Genome Med. 2019;11:87.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Tran E, Ahmadzadeh M, Lu YC, Gros A, Turcotte S, Robbins PF, et al. Immunogenicity of somatic mutations in human gastrointestinal cancers. Science. 2015;350:1387–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Chen F, Zou Z, Du J, Su S, Shao J, Meng F, et al. Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors. J Clin Invest. 2019;129:2056–70.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Cai Z, Su X, Qiu L, Li Z, Li X, Dong X, et al. Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion. Mol Cancer. 2021;20:164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Buonaguro L, Petrizzo A, Tornesello ML, Buonaguro FM. Translating tumor antigens into cancer vaccines. Clin Vaccine Immunol. 2011;18:23–34.

    Article  CAS  PubMed  Google Scholar 

  109. van der Burg SH. Correlates of immune and clinical activity of novel cancer vaccines. Semin Immunol. 2018;39:119–36.

    Article  PubMed  Google Scholar 

  110. Asahara S, Takeda K, Yamao K, Maguchi H, Yamaue H. Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer. J Transl Med. 2013;11:291.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Okuno K, Sugiura F, Inoue K, Sukegawa Y. Clinical trial of a 7-peptide cocktail vaccine with oral chemotherapy for patients with metastatic colorectal cancer. Anticancer Res. 2014;34:3045–52.

    CAS  PubMed  Google Scholar 

  112. Ishikawa H, Imano M, Shiraishi O, Yasuda A, Peng YF, Shinkai M, et al. Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer. Gastric Cancer. 2014;17:173–80.

    Article  CAS  PubMed  Google Scholar 

  113. Khong HT, Restifo NP. Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat Immunol. 2002;3:999–1005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. McCann KJ, Mander A, Cazaly A, Chudley L, Stasakova J, Thirdborough S, et al. Targeting carcinoembryonic antigen with DNA vaccination: on-target adverse events link with immunologic and clinical outcomes. Clin Cancer Res. 2016;22:4827–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroaki Nagano.

Ethics declarations

Conflict of interest

Nobuaki Suzuki and his co-authors have no conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Suzuki, N., Shindo, Y., Nakajima, M. et al. Current status of vaccine immunotherapy for gastrointestinal cancers. Surg Today (2023). https://doi.org/10.1007/s00595-023-02773-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00595-023-02773-y

Keywords

Navigation