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Single-cell imaging of T cell immunotherapy responses in vivo
T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution in vivo. Here, optically clear immunocompromi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383813/ https://www.ncbi.nlm.nih.gov/pubmed/34415995 http://dx.doi.org/10.1084/jem.20210314 |
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author | Yan, Chuan Yang, Qiqi Zhang, Songfa Millar, David G. Alpert, Eric J. Do, Daniel Veloso, Alexandra Brunson, Dalton C. Drapkin, Benjamin J. Stanzione, Marcello Scarfò, Irene Moore, John C. Iyer, Sowmya Qin, Qian Wei, Yun McCarthy, Karin M. Rawls, John F. Dyson, Nick J. Cobbold, Mark Maus, Marcela V. Langenau, David M. |
author_facet | Yan, Chuan Yang, Qiqi Zhang, Songfa Millar, David G. Alpert, Eric J. Do, Daniel Veloso, Alexandra Brunson, Dalton C. Drapkin, Benjamin J. Stanzione, Marcello Scarfò, Irene Moore, John C. Iyer, Sowmya Qin, Qian Wei, Yun McCarthy, Karin M. Rawls, John F. Dyson, Nick J. Cobbold, Mark Maus, Marcela V. Langenau, David M. |
author_sort | Yan, Chuan |
collection | PubMed |
description | T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution in vivo. Here, optically clear immunocompromised zebrafish were engrafted with fluorescent-labeled human cancers along with chimeric antigen receptor T (CAR T) cells, bispecific T cell engagers (BiTEs), and antibody peptide epitope conjugates (APECs), allowing real-time single-cell visualization of T cell–based immunotherapies in vivo. This work uncovered important differences in the kinetics of T cell infiltration, tumor cell engagement, and killing between these immunotherapies and established early endpoint analysis to predict therapy responses. We also established EGFR-targeted immunotherapies as a powerful approach to kill rhabdomyosarcoma muscle cancers, providing strong preclinical rationale for assessing a wider array of T cell immunotherapies in this disease. |
format | Online Article Text |
id | pubmed-8383813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-83838132021-09-01 Single-cell imaging of T cell immunotherapy responses in vivo Yan, Chuan Yang, Qiqi Zhang, Songfa Millar, David G. Alpert, Eric J. Do, Daniel Veloso, Alexandra Brunson, Dalton C. Drapkin, Benjamin J. Stanzione, Marcello Scarfò, Irene Moore, John C. Iyer, Sowmya Qin, Qian Wei, Yun McCarthy, Karin M. Rawls, John F. Dyson, Nick J. Cobbold, Mark Maus, Marcela V. Langenau, David M. J Exp Med Article T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution in vivo. Here, optically clear immunocompromised zebrafish were engrafted with fluorescent-labeled human cancers along with chimeric antigen receptor T (CAR T) cells, bispecific T cell engagers (BiTEs), and antibody peptide epitope conjugates (APECs), allowing real-time single-cell visualization of T cell–based immunotherapies in vivo. This work uncovered important differences in the kinetics of T cell infiltration, tumor cell engagement, and killing between these immunotherapies and established early endpoint analysis to predict therapy responses. We also established EGFR-targeted immunotherapies as a powerful approach to kill rhabdomyosarcoma muscle cancers, providing strong preclinical rationale for assessing a wider array of T cell immunotherapies in this disease. Rockefeller University Press 2021-08-20 /pmc/articles/PMC8383813/ /pubmed/34415995 http://dx.doi.org/10.1084/jem.20210314 Text en © 2021 Yan et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yan, Chuan Yang, Qiqi Zhang, Songfa Millar, David G. Alpert, Eric J. Do, Daniel Veloso, Alexandra Brunson, Dalton C. Drapkin, Benjamin J. Stanzione, Marcello Scarfò, Irene Moore, John C. Iyer, Sowmya Qin, Qian Wei, Yun McCarthy, Karin M. Rawls, John F. Dyson, Nick J. Cobbold, Mark Maus, Marcela V. Langenau, David M. Single-cell imaging of T cell immunotherapy responses in vivo |
title | Single-cell imaging of T cell immunotherapy responses in vivo |
title_full | Single-cell imaging of T cell immunotherapy responses in vivo |
title_fullStr | Single-cell imaging of T cell immunotherapy responses in vivo |
title_full_unstemmed | Single-cell imaging of T cell immunotherapy responses in vivo |
title_short | Single-cell imaging of T cell immunotherapy responses in vivo |
title_sort | single-cell imaging of t cell immunotherapy responses in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383813/ https://www.ncbi.nlm.nih.gov/pubmed/34415995 http://dx.doi.org/10.1084/jem.20210314 |
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