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© Research
Publication : The Journal of experimental medicine

Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of experimental medicine - 01 Apr 2019

Cazaux M, Grandjean CL, Lemaître F, Garcia Z, Beck RJ, Milo I, Postat J, Beltman JB, Cheadle EJ, Bousso P

Link to Pubmed [PMID] – 30936262

J. Exp. Med. 2019 May;216(5):1038-1049

CAR T cells represent a potentially curative strategy for B cell malignancies. However, the outcome and dynamics of CAR T cell interactions in distinct anatomical sites are poorly understood. Using intravital imaging, we tracked interactions established by anti-CD19 CAR T cells in B cell lymphoma-bearing mice. Circulating targets trapped CAR T cells in the lungs, reducing their access to lymphoid organs. In the bone marrow, tumor apoptosis was largely due to CAR T cells that engaged, killed, and detached from their targets within 25 min. Notably, not all CAR T cell contacts elicited calcium signaling or killing while interacting with tumors, uncovering extensive functional heterogeneity. Mathematical modeling revealed that direct killing was sufficient for tumor regression. Finally, antigen-loss variants emerged in the bone marrow, but not in lymph nodes, where CAR T cell cytotoxic activity was reduced. Our results identify a previously unappreciated level of diversity in the outcomes of CAR T cell interactions in vivo, with important clinical implications.

https://www.ncbi.nlm.nih.gov/pubmed/30936262