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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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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. |
format | Online Article Text |
id | pubmed-10470615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
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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