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Vaccines and immune checkpoint inhibitors: a promising combination strategy in gastrointestinal cancers

    Babar Bashir‡

    Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA

    Departments of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    John C Flickinger‡

    Departments of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA

    ‡Authors contributed equally

    Search for more papers by this author

    &
    Adam E Snook

    *Author for correspondence: Tel.: +215 503 7445;

    E-mail Address: adam.snook@jefferson.edu

    Departments of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA

    Published Online:https://doi.org/10.2217/imt-2021-0012

    Tweetable abstract

    US FDA-approved immune checkpoint inhibitors have limited efficacy for gastrointestinal cancers such as #colorectalcancer and #pancreaticcancer. Could combinations with experimental cancer ‘vaccines’ be the key?

    References

    • 1. Mandal R, Samstein RM, Lee K-W et al. Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response. Science 364(6439), 485–491 (2019).
    • 2. André T, Shiu K-K, Kim TW et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N. Engl. J. Med. 383(23), 2207–2218 (2020).
    • 3. Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N. Engl. J. Med. 377(25), 2500–2501 (2017).
    • 4. Chalmers ZR, Connelly CF, Fabrizio D et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 9(1), 34 (2017).
    • 5. Marabelle A, Fakih M, Lopez J et al. Association of tumor mutational burden with outcomes in patients with advanced solid tumors treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, Phase II KEYNOTE-158 study. Lancet Oncol. 21(10), 1353–1365 (2020).
    • 6. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines – a new era in vaccinology. Nat. Rev. Drug Discov. 17(4), 261–279 (2018).
    • 7. Aleksic M, Liddy N, Molloy PE et al. Different affinity windows for virus and cancer-specific T-cell receptors: implications for therapeutic strategies. Eur. J. Immunol. 42(12), 3174–3179 (2012).
    • 8. Tumeh PC, Harview CL, Yearley JH et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515(7528), 568–571 (2014).
    • 9. Zheng L, Ding D, Edil BH et al. Vaccine-induced intratumoral lymphoid aggregates correlate with survival following treatment with a neoadjuvant and adjuvant vaccine in patients with resectable pancreatic adenocarcinoma. Clin. Cancer Res. 27, 1278–86 (2021).
    • 10. Sahin U, Derhovanessian E, Miller M et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547(7662), 222–226 (2017).
    • 11. Ott PA, Hu Z, Keskin DB et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547(7662), 217–221 (2017).
    • 12. Fang Y, Mo F, Shou J et al. A pan-cancer clinical study of personalized neoantigen vaccine monotherapy in treating patients with various types of advanced solid tumors. Clin. Cancer Res. 26(17), 4511–4520 (2020).
    • 13. Cafri G, Gartner JJ, Zaks T et al. mRNA vaccine-induced neoantigen-specific T cell immunity in patients with gastrointestinal cancer. J. Clin. Invest. 130(11), 5976–5988 (2020).
    • 14. Markowitz S, Wang J, Myeroff L et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 268(5215), 1336–1338 (1995).
    • 15. Kloor M, Reuschenbach M, Pauligk C et al. A frameshift peptide neoantigen-based vaccine for mismatch repair-deficient cancers: a Phase I/IIa clinical trial. Clin. Cancer Res. 26(17), 4503–4510 (2020).
    • 16. Leoni G, D'Alise AM, Cotugno G et al. A genetic vaccine encoding shared cancer neoantigens to treat tumors with microsatellite instability. Cancer Res. 80(18), 3972–3982 (2020).
    • 17. Newey A, Griffiths B, Michaux J et al. Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment. J. Immunother. Cancer 7(1), 309 (2019).
    • 18. Lind H, Gameiro SR, Jochems C et al. Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances. J. Immunother. Cancer 8(1), e000433(2020).
    • 19. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature 541(7637), 321–330 (2017).
    • 20. Tran E, Robbins PF, Lu Y-C et al. T-Cell transfer therapy targeting mutant KRAS in cancer. N. Engl. J. Med. 375(23), 2255–2262 (2016).