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Single-cell imaging of T cell immunotherapy responses in vivo
来源: | 作者:Chuan Yan 1 2 3 4, Qiqi Yang 1 2 3 4, Songfa Zhang 2, David G Millar 2, Eric J Alpert 1 2 3 4, Daniel Do 1 2 3 4, Alexandra Veloso 1 2 3 4, Dalton C Brunson 1 2 3 4, Benjamin J Drapkin 2, Marcello Stanzione 2, Irene Scarfò 2, John C Moore 1 2 3 4, Sowmya | 发布时间: 2021-09-17 | 179 次浏览 | 分享到:

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.