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 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.
Yan, C; Yang, Q; Zhang, S; Millar, DG; Alpert, EJ; Do, D; Veloso, A; Brunson, DC; Drapkin, BJ; Stanzione, M; Scarfò, I; Moore, JC; Iyer, S; Qin, Q; Wei, Y; McCarthy, KM; Rawls, JF; Dyson, NJ; Cobbold, M; Maus, MV; Langenau, DM
Volume / Issue
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)