Single-cell imaging of T cell immunotherapy responses in vivo.

Journal Article (Journal 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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • October 4, 2021

Published In

Volume / Issue

  • 218 / 10

PubMed ID

  • 34415995

Pubmed Central ID

  • PMC8383813

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20210314

Language

  • eng

Conference Location

  • United States