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

Publication ,  Journal Article
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 ...
Published in: J Exp Med
October 4, 2021

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.

Duke Scholars

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Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

October 4, 2021

Volume

218

Issue

10

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Temozolomide
  • T-Lymphocytes
  • Single-Cell Analysis
  • Rhabdomyosarcoma
  • Piperazines
  • Phthalazines
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yan, C., Yang, Q., Zhang, S., Millar, D. G., Alpert, E. J., Do, D., … Langenau, D. M. (2021). Single-cell imaging of T cell immunotherapy responses in vivo. J Exp Med, 218(10). https://doi.org/10.1084/jem.20210314
Yan, Chuan, Qiqi Yang, Songfa Zhang, David G. Millar, Eric J. Alpert, Daniel Do, Alexandra Veloso, et al. “Single-cell imaging of T cell immunotherapy responses in vivo.J Exp Med 218, no. 10 (October 4, 2021). https://doi.org/10.1084/jem.20210314.
Yan C, Yang Q, Zhang S, Millar DG, Alpert EJ, Do D, et al. Single-cell imaging of T cell immunotherapy responses in vivo. J Exp Med. 2021 Oct 4;218(10).
Yan, Chuan, et al. “Single-cell imaging of T cell immunotherapy responses in vivo.J Exp Med, vol. 218, no. 10, Oct. 2021. Pubmed, doi:10.1084/jem.20210314.
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. Single-cell imaging of T cell immunotherapy responses in vivo. J Exp Med. 2021 Oct 4;218(10).

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

October 4, 2021

Volume

218

Issue

10

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Temozolomide
  • T-Lymphocytes
  • Single-Cell Analysis
  • Rhabdomyosarcoma
  • Piperazines
  • Phthalazines