Journal Club de l’AST/AJT – 24 novembre : Dre Megan Levings

L’American Society of Transplantation (AST) et l’American Journal of Transplantation (AJT) invitent la communauté de transplantation à rejoindre le Journal Club basé sur cet article publié dans Science Translational Medicine en août 2020 : « Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells. » (en anglais)

24 novembre 2020 à 14h00 HE – Inscrivez-vous ici.
Conférencière :
  • Megan Levings, PhD • University of British Columbia, Vancouver, BC
Modératrice :
  • Olivia Martinez, PhD • Stanford University, Stanford, CA
Invités Questions-Réponses :
  • Nicholas Dawson, PhD • University of British Columbia, Vancouver, BC
  • Isaac Rosado-Sánchez, PhD • BC Children’s Hospital Research Institute, Vancouver, BC

Les Journal clubs sont gratuits pour les membres et les non-membres. Une pré-inscription est nécessaire.

Résumé de l’article (en anglais)

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.

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