A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope

Abstract 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;...

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Autores principales:	Adam M. Swartz, Kendra L. Congdon, Smita K. Nair, Qi-Jing Li, James E. Herndon, Carter M. Suryadevara, Katherine A. Riccione, Gary E. Archer, Pamela K. Norberg, Luis A. Sanchez-Perez, John H. Sampson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/630d5dbd82df4a1bb95d08b2e6228b95
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spelling	oai:doaj.org-article:630d5dbd82df4a1bb95d08b2e6228b952021-12-02T15:23:47ZA conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope10.1038/s41541-020-00273-52059-0105https://doaj.org/article/630d5dbd82df4a1bb95d08b2e6228b952021-01-01T00:00:00Zhttps://doi.org/10.1038/s41541-020-00273-5https://doaj.org/toc/2059-0105Abstract 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.Adam M. SwartzKendra L. CongdonSmita K. NairQi-Jing LiJames E. HerndonCarter M. SuryadevaraKatherine A. RiccioneGary E. ArcherPamela K. NorbergLuis A. Sanchez-PerezJohn H. SampsonNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Adam M. Swartz Kendra L. Congdon Smita K. Nair Qi-Jing Li James E. Herndon Carter M. Suryadevara Katherine A. Riccione Gary E. Archer Pamela K. Norberg Luis A. Sanchez-Perez John H. Sampson A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope
description	Abstract 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.
format	article
author	Adam M. Swartz Kendra L. Congdon Smita K. Nair Qi-Jing Li James E. Herndon Carter M. Suryadevara Katherine A. Riccione Gary E. Archer Pamela K. Norberg Luis A. Sanchez-Perez John H. Sampson
author_facet	Adam M. Swartz Kendra L. Congdon Smita K. Nair Qi-Jing Li James E. Herndon Carter M. Suryadevara Katherine A. Riccione Gary E. Archer Pamela K. Norberg Luis A. Sanchez-Perez John H. Sampson
author_sort	Adam M. Swartz
title	A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope
title_short	A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope
title_full	A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope
title_fullStr	A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope
title_full_unstemmed	A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope
title_sort	conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an mhc class i-restricted neoepitope
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/630d5dbd82df4a1bb95d08b2e6228b95
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A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope

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