AST/AJT Journal Club November 24: Dr. Megan Levings
The American Society of Transplantation (AST) and the American Journal of Transplantation (AJT) invite the transplant community to join the Journal Club based on this article published in Science Translational Medicine in August 2020: “Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells.”
November 24, 2020 at 2:00pm EST – Register here.
- Megan Levings, PhD • University of British Columbia, Vancouver, BC
- Olivia Martinez, PhD • Stanford University, Stanford, CA
- Nicholas Dawson, PhD • University of British Columbia, Vancouver, BC
- Isaac Rosado-Sánchez, PhD • BC Children’s Hospital Research Institute, Vancouver, BC
Journal clubs are free for both members and non-members. Pre-registration is required.
Antigen-specific regulatory T cells (Tregs) engineered with chimeric antigen receptors (CARs) are a potent immunosuppressive cellular therapy in multiple disease models and could overcome shortcomings of polyclonal Treg therapy. CAR therapy was initially developed with conventional T cells, which have different signaling requirements than do Tregs. To date, most of the CAR Treg studies used second-generation CARs, encoding a CD28 or 4-1BB co-receptor signaling domain and CD3ζ, but it was not known if this CAR design was optimal for Tregs. Using a human leukocyte antigen–A2–specific CAR platform and human Tregs, we compared 10 CARs with different co-receptor signaling domains and systematically tested their function and CAR-stimulated gene expression profile. Tregs 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 Tregs can be leveraged to optimize CAR design for use in antigen-specific Treg therapy.