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dc.contributor.authorCazaux, M
dc.contributor.authorGrandjean, CL
dc.contributor.authorLemaitre, F
dc.contributor.authorGarcia, Z
dc.contributor.authorBeck, RJ
dc.contributor.authorMilo, I
dc.contributor.authorPostat, J
dc.contributor.authorBeltman, JB
dc.contributor.authorCheadle, Eleanor J
dc.contributor.authorBousso, P
dc.date.accessioned2019-04-29T09:48:54Z
dc.date.available2019-04-29T09:48:54Z
dc.date.issued2019en
dc.identifier.citationCazaux 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.pmid30936262en
dc.identifier.doi10.1084/jem.20182375en
dc.identifier.urihttp://hdl.handle.net/10541/621736
dc.description.abstractCAR 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.isoenen
dc.relation.urlhttps://dx.doi.org/10.1084/jem.20182375en
dc.titleSingle-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneityen
dc.typeArticleen
dc.contributor.departmentDynamics of Immune Responses Unit, Equipe Labellisee Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, Franceen
dc.identifier.journalThe Journal of Experimental Medicineen
dc.description.noteen]


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