Single-cell imaging of T cell immunotherapy responses in vivo

Chuan Yan, Qiqi Yang, Songfa Zhang, David G. Millar, Eric J. Alpert, Daniel Do, Alexandra Veloso, Dalton C. Brunson, Benjamin J. Drapkin, Marcello Stanzione, Irene Scarfò, John C. Moore, Sowmya Iyer, Qian Qin, Yun Wei, Karin M. McCarthy, John F. Rawls, Nick J. Dyson, Mark Cobbold, Marcela V. MausDavid M. Langenau

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere20210314
JournalJournal of Experimental Medicine
Volume218
Issue number10
DOIs
StatePublished - Aug 20 2021
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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