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05.05.22

TCR-Independent Activation with Src- Kinase Inhibitor Improves CAR T Cell Attributes

by ASTCT Science Highlights

Lamture G, Baer A, Fischer JW, et al. TCR-Independent Activation in Presence of a Src-Family Kinase Inhibitor Improves CAR-T Cell Product Attributes. Journal of Immunotherapy. 2022; 45 (3): 139 (doi: 10.1097/CJI.0000000000000402).

Manufacturing chimeric antigen receptor (CAR) T cells without engaging the T-cell receptor (TCR), but in the presence of an Src-kinase inhibitor (SKI), avoids some of the shortcomings associated with TCR-dependent (TCRD) activation. Researchers discovered this when comparing the novel approach with the established technique. Compared with TCRD activation, TCR-independent (TCRI) activation in the presence of an SKI significantly improved CAR T cell expansion. Greater volumes of naive and central memory cells were generated, along with lower volumes of effector cells in the CAR T cell product, suggesting better persistence and improved in vivo functionality. TCRI also reduced markers of T-cell activation, differentiation, and exhaustion — which can affect CAR T cell product quality and in vivo potency, if allowed to go unchecked — more effectively than TCRD. Further study is warranted, the investigators note, "to better understand mechanisms for improvement of these product quality attributes, which may help develop strategies to improve CAR T cell manufacturing, safety, efficacy and reduce manufacturing failures."

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ASTCT

American Society for Transplantation
and Cellular Therapy

330 North Wabash Avenue, Suite 2000
Chicago, IL 60611, USA
Phone: (312) 321-6820
Fax: (312) 673-6733

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