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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
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.
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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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