AST/AJT Journal Club: "Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells."

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"Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells."
(Science Translational Medicine; 19 Aug 2020: Vol. 12, Issue 557, eaaz3866; DOI: 10.1126/scitranslmed.aaz3866)

In this article:
Using a human leukocyte antigen–A2–specific CAR platform and human T_regs, [the authors] compared 10 CARs with different co-receptor signaling domains and systematically tested their function and CAR-stimulated gene expression profile. T_regs expressing a CAR encoding CD28wt were markedly superior to all other CARs tested in an in vivo model of graft-versus-host disease. In vitro assays revealed stable expression of Helios and an ability to suppress CD80 expression on dendritic cells as key in vitro predictors of in vivo function. This comprehensive study of CAR signaling domain variants in T_regs can be leveraged to optimize CAR design for use in antigen-specific T_reg therapy.

Speaker:
Megan Levings, PhD • University of British Columbia, Vancouver, BC

Moderator:
Olivia Martinez, PhD • Stanford University, Stanford, CA

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