2019
DOI: 10.1172/jci.insight.124430
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Sensitive and adaptable pharmacological control of CAR T cells through extracellular receptor dimerization

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Cited by 58 publications
(84 citation statements)
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“…Irrespective of mechanism, these results demonstrate that cessation of CAR signaling is a potent maneuver that results in augmented function in cell populations that are transitioning to exhaustion or in those already imprinted with hallmark features of exhaustion, and is distinct from that which can be achieved with PD-1/PD-L1 blockade. Advances in synthetic biology have enabled the development of several tunable CAR platforms which have been optimized to mitigate CAR-mediated toxicity (Bejestani et al, 2017;Cho et al, 2018;Leung et al, 2019;Rodgers et al, 2016;Wu et al, 2015). Our data suggest that such platforms, including the DD-CAR system described here, may enhance CAR-T cell potency as a result of temporal control of CAR-T cell signaling.…”
Section: Discussionmentioning
confidence: 70%
“…Irrespective of mechanism, these results demonstrate that cessation of CAR signaling is a potent maneuver that results in augmented function in cell populations that are transitioning to exhaustion or in those already imprinted with hallmark features of exhaustion, and is distinct from that which can be achieved with PD-1/PD-L1 blockade. Advances in synthetic biology have enabled the development of several tunable CAR platforms which have been optimized to mitigate CAR-mediated toxicity (Bejestani et al, 2017;Cho et al, 2018;Leung et al, 2019;Rodgers et al, 2016;Wu et al, 2015). Our data suggest that such platforms, including the DD-CAR system described here, may enhance CAR-T cell potency as a result of temporal control of CAR-T cell signaling.…”
Section: Discussionmentioning
confidence: 70%
“…To address the lack of control and tumor specificity associated with CAR-T cells, several promising strategies have been developed including CARs for combinatorial antigen recognition [8][9][10][11][12][13][14] , affinity-tuned CARs to minimize killing of healthy cells expressing low levels of target antigen [15][16][17][18][19][20] and CARs whose function can be regulated by administration of small molecules or soluble proteins 10,[21][22][23][24][25][26][27][28][29] . Despite these important advances, there is still a need for improvement.…”
mentioning
confidence: 99%
“…However, due to its immunosuppressive activity, rapamycin is considered to be suboptimal. A very recent preclinical CAR study showed promising results with lower concentrations of this drug ( 39 ). Nevertheless, if available, a safe compound without any immunocompromising effect—like A1120—would be preferred, especially for immunotherapeutic applications.…”
Section: Discussionmentioning
confidence: 99%