Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity
dc.contributor.author | Cazaux, M | |
dc.contributor.author | Grandjean, CL | |
dc.contributor.author | Lemaitre, F | |
dc.contributor.author | Garcia, Z | |
dc.contributor.author | Beck, RJ | |
dc.contributor.author | Milo, I | |
dc.contributor.author | Postat, J | |
dc.contributor.author | Beltman, JB | |
dc.contributor.author | Cheadle, Eleanor J | |
dc.contributor.author | Bousso, P | |
dc.date.accessioned | 2019-04-29T09:48:54Z | |
dc.date.available | 2019-04-29T09:48:54Z | |
dc.date.issued | 2019 | en |
dc.identifier.citation | Cazaux M, Grandjean CL, Lemaitre F, Garcia Z, Beck RJ, Milo I, et al. Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity. J Exp Med. 2019 Apr 1. | en |
dc.identifier.pmid | 30936262 | en |
dc.identifier.doi | 10.1084/jem.20182375 | en |
dc.identifier.uri | http://hdl.handle.net/10541/621736 | |
dc.description.abstract | 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. | en |
dc.language.iso | en | en |
dc.relation.url | https://dx.doi.org/10.1084/jem.20182375 | en |
dc.title | Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity | en |
dc.type | Article | en |
dc.contributor.department | Dynamics of Immune Responses Unit, Equipe Labellisee Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France | en |
dc.identifier.journal | The Journal of Experimental Medicine | en |
dc.description.note | en] |