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Isolation and characterization of NY-ESO-1–specific T cell receptors restricted on various MHC molecules
Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. Due to the prevalence of the HLA-A2 MHC class I supertype in most human populations, the majority of TCR gene therapy trials targeting public antigens have employed HLA-A2–restricted TC...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233129/ https://www.ncbi.nlm.nih.gov/pubmed/30348802 http://dx.doi.org/10.1073/pnas.1810653115 |
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author | Bethune, Michael T. Li, Xiao-Hua Yu, Jiaji McLaughlin, Jami Cheng, Donghui Mathis, Colleen Moreno, Blanca Homet Woods, Katherine Knights, Ashley J. Garcia-Diaz, Angel Wong, Stephanie Hu-Lieskovan, Siwen Puig-Saus, Cristina Cebon, Jonathan Ribas, Antoni Yang, Lili Witte, Owen N. Baltimore, David |
author_facet | Bethune, Michael T. Li, Xiao-Hua Yu, Jiaji McLaughlin, Jami Cheng, Donghui Mathis, Colleen Moreno, Blanca Homet Woods, Katherine Knights, Ashley J. Garcia-Diaz, Angel Wong, Stephanie Hu-Lieskovan, Siwen Puig-Saus, Cristina Cebon, Jonathan Ribas, Antoni Yang, Lili Witte, Owen N. Baltimore, David |
author_sort | Bethune, Michael T. |
collection | PubMed |
description | Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. Due to the prevalence of the HLA-A2 MHC class I supertype in most human populations, the majority of TCR gene therapy trials targeting public antigens have employed HLA-A2–restricted TCRs, limiting this approach to those patients expressing this allele. For these patients, TCR gene therapy trials have resulted in both tantalizing successes and lethal adverse events, underscoring the need for careful selection of antigenic targets. Broad and safe application of public antigen-targeted TCR gene therapies will require (i) selecting public antigens that are highly tumor-specific and (ii) targeting multiple epitopes derived from these antigens by obtaining an assortment of TCRs restricted by multiple common MHC alleles. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we pilot an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2. |
format | Online Article Text |
id | pubmed-6233129 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-62331292018-11-14 Isolation and characterization of NY-ESO-1–specific T cell receptors restricted on various MHC molecules Bethune, Michael T. Li, Xiao-Hua Yu, Jiaji McLaughlin, Jami Cheng, Donghui Mathis, Colleen Moreno, Blanca Homet Woods, Katherine Knights, Ashley J. Garcia-Diaz, Angel Wong, Stephanie Hu-Lieskovan, Siwen Puig-Saus, Cristina Cebon, Jonathan Ribas, Antoni Yang, Lili Witte, Owen N. Baltimore, David Proc Natl Acad Sci U S A PNAS Plus Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. Due to the prevalence of the HLA-A2 MHC class I supertype in most human populations, the majority of TCR gene therapy trials targeting public antigens have employed HLA-A2–restricted TCRs, limiting this approach to those patients expressing this allele. For these patients, TCR gene therapy trials have resulted in both tantalizing successes and lethal adverse events, underscoring the need for careful selection of antigenic targets. Broad and safe application of public antigen-targeted TCR gene therapies will require (i) selecting public antigens that are highly tumor-specific and (ii) targeting multiple epitopes derived from these antigens by obtaining an assortment of TCRs restricted by multiple common MHC alleles. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we pilot an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2. National Academy of Sciences 2018-11-06 2018-10-22 /pmc/articles/PMC6233129/ /pubmed/30348802 http://dx.doi.org/10.1073/pnas.1810653115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | PNAS Plus Bethune, Michael T. Li, Xiao-Hua Yu, Jiaji McLaughlin, Jami Cheng, Donghui Mathis, Colleen Moreno, Blanca Homet Woods, Katherine Knights, Ashley J. Garcia-Diaz, Angel Wong, Stephanie Hu-Lieskovan, Siwen Puig-Saus, Cristina Cebon, Jonathan Ribas, Antoni Yang, Lili Witte, Owen N. Baltimore, David Isolation and characterization of NY-ESO-1–specific T cell receptors restricted on various MHC molecules |
title | Isolation and characterization of NY-ESO-1–specific T cell receptors restricted on various MHC molecules |
title_full | Isolation and characterization of NY-ESO-1–specific T cell receptors restricted on various MHC molecules |
title_fullStr | Isolation and characterization of NY-ESO-1–specific T cell receptors restricted on various MHC molecules |
title_full_unstemmed | Isolation and characterization of NY-ESO-1–specific T cell receptors restricted on various MHC molecules |
title_short | Isolation and characterization of NY-ESO-1–specific T cell receptors restricted on various MHC molecules |
title_sort | isolation and characterization of ny-eso-1–specific t cell receptors restricted on various mhc molecules |
topic | PNAS Plus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233129/ https://www.ncbi.nlm.nih.gov/pubmed/30348802 http://dx.doi.org/10.1073/pnas.1810653115 |
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