Subhash Tripathi, PhD, on Generating In Vivo CARs With A2-CAR-CISC EngTreg Cells

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The senior researcher at Seattle Children’s discussed the development and validation of A2-CAR-CISC EngTreg cells.

"Altogether, our A2-CAR engineered system for the first time demonstrated that we can also provide endogenous production of CAR and successfully generated this A2-CAR engineered Treg project using LV and dual edit approach. And overall, what we can say is that this platform may have implications of treating or use in transplant, autoimmunity or other inflammatory diseases... I think it is a very exciting field, with providing antigen assist to CARs we can not only treat a particular but a broad range of immune diseases."

The lab of David Rawlings, MD, at Seattle Children’s Hospital, has been working on developing and improving regulatory T-cell (Treg) therapies for therapeutic use in transplantation, autoimmune and/or autoinflammatory disease, including diabetes type 1 and multiple sclerosis, among others. These cells are termed CAR-CISC EngTreg cells. One such product from this research is A2-CAR-CISC EngTreg cells, data from the development and validation of which were presented by Subhash Tripathi, PhD, senior researcher at Seattle Children’s and a member of Rawlings' lab, at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland.

A2-CAR-CISC EngTreg cells are designed to generate HLA-A*02 antibody-based chimeric antigen receptor (CAR) Treg cells in vivo by use of dual homology-directed-repair gene editing. The cells demonstrated specific targeting and no cases of graft versus host disease in early mice studies. CGTLive spoke to Tripathi to learn more about the development of CAR-CISC EngTreg cells, and specifically, developing antigen specific for HLA-A*02 cells, A2-CAR-CISC EngTreg cells. He gave an overview of how these cells were generated and their validation in early mouse studies.

REFERENCE
Tripathi SK, Dahl NP, Grimm A, et al. HLA-A2 CAR/IL-2-CISC Engineered Treg Exhibit Robust In Vitro and In Vivo Efficacy. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #90
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