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

  • External authors:
  • Marine Cazaux
  • Capucine L Grandjean
  • Fabrice Lemaître
  • Zacarias Garcia
  • Richard J Beck
  • Idan Milo
  • Jérémy Postat
  • Joost B Beltman
  • Philippe Bousso

Standard

Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity. / Cazaux, Marine; Grandjean, Capucine L; Lemaître, Fabrice; Garcia, Zacarias; Beck, Richard J; Milo, Idan; Postat, Jérémy; Beltman, Joost B; Cheadle, Eleanor J; Bousso, Philippe.

In: The Journal of experimental medicine, 2019.

Research output: Contribution to journalArticlepeer-review

Harvard

Cazaux, M, Grandjean, CL, Lemaître, F, Garcia, Z, Beck, RJ, Milo, I, Postat, J, Beltman, JB, Cheadle, EJ & Bousso, P 2019, 'Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity', The Journal of experimental medicine. https://doi.org/10.1084/jem.20182375

APA

Cazaux, M., Grandjean, C. L., Lemaître, F., Garcia, Z., Beck, R. J., Milo, I., Postat, J., Beltman, J. B., Cheadle, E. J., & Bousso, P. (2019). Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity. The Journal of experimental medicine. https://doi.org/10.1084/jem.20182375

Vancouver

Cazaux M, Grandjean CL, Lemaître 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. The Journal of experimental medicine. 2019. https://doi.org/10.1084/jem.20182375

Author

Cazaux, Marine ; Grandjean, Capucine L ; Lemaître, Fabrice ; Garcia, Zacarias ; Beck, Richard J ; Milo, Idan ; Postat, Jérémy ; Beltman, Joost B ; Cheadle, Eleanor J ; Bousso, Philippe. / Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity. In: The Journal of experimental medicine. 2019.

Bibtex

@article{79dea714dd65407088880ecab5f66514,
title = "Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity",
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.",
author = "Marine Cazaux and Grandjean, {Capucine L} and Fabrice Lema{\^i}tre and Zacarias Garcia and Beck, {Richard J} and Idan Milo and J{\'e}r{\'e}my Postat and Beltman, {Joost B} and Cheadle, {Eleanor J} and Philippe Bousso",
note = "{\textcopyright} 2019 Cazaux et al.",
year = "2019",
doi = "10.1084/jem.20182375",
language = "English",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",

}

RIS

TY - JOUR

T1 - Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity

AU - Cazaux, Marine

AU - Grandjean, Capucine L

AU - Lemaître, Fabrice

AU - Garcia, Zacarias

AU - Beck, Richard J

AU - Milo, Idan

AU - Postat, Jérémy

AU - Beltman, Joost B

AU - Cheadle, Eleanor J

AU - Bousso, Philippe

N1 - © 2019 Cazaux et al.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1084/jem.20182375

DO - 10.1084/jem.20182375

M3 - Article

C2 - 30936262

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

ER -