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- Single-cell_imaging_of_CAR_T_cell_activity
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Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity
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.
Show less- All authors
- Cazaux, M.; Grandjean, C.L.; Lemaitre, Fabrice; Garcia, Z.; Beck, R.J.; Milo, I.; Postat, J.; Beltman, J.B.; Cheadle, E.J.; Bousso, P.
- Date
- 2019-05-31
- Journal
- Journal of Experimental Medicine
- Volume
- 216
- Issue
- 5
- Pages
- 1038 - 1049