PUBLICATION
Single-cell imaging of T cell immunotherapy responses in vivo
- Authors
- Yan, C., Yang, Q., Zhang, S., Millar, D.G., Alpert, E.J., Do, D., Veloso, A., Brunson, D.C., Drapkin, B.J., Stanzione, M., Scarfò, I., Moore, J.C., Iyer, S., Qin, Q., Wei, Y., McCarthy, K.M., Rawls, J.F., Dyson, N.J., Cobbold, M., Maus, M.V., Langenau, D.M.
- ID
- ZDB-PUB-210821-10
- Date
- 2021
- Source
- The Journal of experimental medicine 218(10): (Journal)
- Registered Authors
- Langenau, David, Rawls, John F.
- Keywords
- none
- Datasets
- GEO:GSE179401
- MeSH Terms
-
- Adolescent
- Adult
- Animals
- Animals, Genetically Modified
- Child
- Child, Preschool
- DNA-Binding Proteins/genetics
- ErbB Receptors/immunology
- Female
- Humans
- Immunotherapy/methods*
- Immunotherapy, Adoptive
- Interleukin Receptor Common gamma Subunit/genetics
- Male
- Mice, Inbred Strains
- Phthalazines/pharmacology
- Piperazines/pharmacology
- Rhabdomyosarcoma/pathology
- Rhabdomyosarcoma/therapy*
- Single-Cell Analysis/methods*
- T-Lymphocytes/immunology
- Temozolomide/pharmacology
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays/methods*
- Zebrafish/genetics*
- Zebrafish Proteins/genetics
- PubMed
- 34415995 Full text @ J. Exp. Med.
Citation
Yan, C., Yang, Q., Zhang, S., Millar, D.G., Alpert, E.J., Do, D., Veloso, A., Brunson, D.C., Drapkin, B.J., Stanzione, M., Scarfò, I., Moore, J.C., Iyer, S., Qin, Q., Wei, Y., McCarthy, K.M., Rawls, J.F., Dyson, N.J., Cobbold, M., Maus, M.V., Langenau, D.M. (2021) Single-cell imaging of T cell immunotherapy responses in vivo. The Journal of experimental medicine. 218(10):.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping