A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope.
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2021-01-18
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Personalized cancer vaccines targeting neoantigens arising from somatic missense mutations are currently being evaluated for the treatment of various cancers due to their potential to elicit a multivalent, tumor-specific immune response. Several cancers express a low number of neoantigens; in these cases, ensuring the immunotherapeutic potential of each neoantigen-derived epitope (neoepitope) is crucial. In this study, we discovered that therapeutic vaccines targeting immunodominant major histocompatibility complex (MHC) I-restricted neoepitopes require a conjoined helper epitope in order to induce a cytotoxic, neoepitope-specific CD8+ T-cell response. Furthermore, we show that the universally immunogenic helper epitope P30 can fulfill this requisite helper function. Remarkably, conjoined P30 was able to unveil immune and antitumor responses to subdominant MHC I-restricted neoepitopes that were, otherwise, poorly immunogenic. Together, these data provide key insights into effective neoantigen vaccine design and demonstrate a translatable strategy using a universal helper epitope that can improve therapeutic responses to MHC I-restricted neoepitopes.
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Swartz, Adam M, Kendra L Congdon, Smita K Nair, Qi-Jing Li, James E Herndon, Carter M Suryadevara, Katherine A Riccione, Gary E Archer, et al. (2021). A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope. NPJ vaccines, 6(1). p. 12. 10.1038/s41541-020-00273-5 Retrieved from https://hdl.handle.net/10161/22510.
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Smita K Nair
I have 22 years of experience in the field of cancer vaccines and immunotherapy and I am an accomplished T cell immunologist. Laboratory website:
https://surgery.duke.edu/immunology-inflammation-immunotherapy-laboratory
Current projects in the Nair Laboratory:
1] Dendritic cell vaccines using tumor-antigen encoding RNA (mRNA, total tumor RNA, amplified tumor mRNA)
2] Local immune receptor modulation using mRNA that encodes for antibodies, receptor-ligands, cytokines, chemokines and toll-like receptors (current target list: CTLA4, GITR, PD1, TIM3, LAG3, OX40 and 41BB)
3] Combination therapies for cancer: cytotoxic therapy (radiation, chemo and oncolytic poliovirus therapy) with dendritic cell-based vaccines and immune checkpoint blockade
4] Adoptive T cell therapy using tumor RNA-transfected dendritic cells to expand tumor-specific T cells ex vivo
5] Adoptive T cell therapy using PSMA CAR (chimeric antigen receptor) RNA-transfected T cells
6] Direct injection of tumor antigen encoding RNA (targeting antigens to dendric cells in vivo using nanoparticles and aptamers)
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