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Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy

T cell reactivity to tumor-specific neoantigens can drive endogenous and therapeutically induced antitumor immunity. However, most tumor-specific neoantigens are unique to each patient (private) and targeting them requires personalized therapy. A smaller subset of neoantigens includes epitopes that...

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Detalles Bibliográficos
Autores principales: Martinov, Tijana, Greenberg, Philip D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470615/
https://www.ncbi.nlm.nih.gov/pubmed/37655310
http://dx.doi.org/10.1146/annurev-cancerbio-061521-082114
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author Martinov, Tijana
Greenberg, Philip D.
author_facet Martinov, Tijana
Greenberg, Philip D.
author_sort Martinov, Tijana
collection PubMed
description T cell reactivity to tumor-specific neoantigens can drive endogenous and therapeutically induced antitumor immunity. However, most tumor-specific neoantigens are unique to each patient (private) and targeting them requires personalized therapy. A smaller subset of neoantigens includes epitopes that span recurrent mutation hotspots, translocations, or gene fusions in oncogenic drivers and tumor suppressors, as well as epitopes that arise from viral oncogenic proteins. Such antigens are likely to be shared across patients (public), uniformly expressed within a tumor, and required for cancer cell survival and fitness. Although a limited number of these public neoantigens are naturally immunogenic, recent studies affirm their clinical utility. In this review, we highlight efforts to target mutant KRAS, mutant p53, and epitopes derived from oncogenic viruses using T cells engineered with off-the-shelf T cell receptors. We also discuss the challenges and strategies to achieving more effective T cell therapies, particularly in the context of solid tumors.
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spelling pubmed-104706152023-08-31 Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy Martinov, Tijana Greenberg, Philip D. Annu Rev Cancer Biol Article T cell reactivity to tumor-specific neoantigens can drive endogenous and therapeutically induced antitumor immunity. However, most tumor-specific neoantigens are unique to each patient (private) and targeting them requires personalized therapy. A smaller subset of neoantigens includes epitopes that span recurrent mutation hotspots, translocations, or gene fusions in oncogenic drivers and tumor suppressors, as well as epitopes that arise from viral oncogenic proteins. Such antigens are likely to be shared across patients (public), uniformly expressed within a tumor, and required for cancer cell survival and fitness. Although a limited number of these public neoantigens are naturally immunogenic, recent studies affirm their clinical utility. In this review, we highlight efforts to target mutant KRAS, mutant p53, and epitopes derived from oncogenic viruses using T cells engineered with off-the-shelf T cell receptors. We also discuss the challenges and strategies to achieving more effective T cell therapies, particularly in the context of solid tumors. 2023 2023-01-25 /pmc/articles/PMC10470615/ /pubmed/37655310 http://dx.doi.org/10.1146/annurev-cancerbio-061521-082114 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.
spellingShingle Article
Martinov, Tijana
Greenberg, Philip D.
Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy
title Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy
title_full Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy
title_fullStr Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy
title_full_unstemmed Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy
title_short Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy
title_sort targeting driver oncogenes and other public neoantigens using t cell receptor–based cellular therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470615/
https://www.ncbi.nlm.nih.gov/pubmed/37655310
http://dx.doi.org/10.1146/annurev-cancerbio-061521-082114
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