Subhash Tripathi, PhD, on Developing Safe, Specific Engineered Treg Cell Therapy

“There are disadvantages associated with current adaptive cell therapies, which are based on natural regulatory T-cells. To cite some of those key technical hurdles, there is a huge rarity of these populations in vivo. So if you get them, you have to scale up for manufacturing, which is very difficult, and then they are very unstable and have plasticity. They have a very poor engraftment in vivo. And sometimes, if you get these cells from patients, they might be defective.”

CAR-CISC EngTreg cells may have therapeutic potential in transplantation, autoimmune and/or autoinflammatory disease, including diabetes type 1 and multiple sclerosis, among others. The lab of David Rawlings, MD, at Seattle Children’s Hospital, has been working on developing and improving regulatory T-cell (Treg) therapies for these uses. A member of the Rawlings lab, Subhash Tripathi, PhD, senior researcher at Seattle Children’s, presented findings from the development and validation of Treg therapies, the final iteration of which was an A2-CAR-CISC EngTreg cell, 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 use dual homology-directed-repair gene editing to generate HLA-A*02 antibody-based chimeric antigen receptor (CAR) Treg cells. Early mice studies demonstrate specific targeting and no cases of graft versus host disease. CGTLive spoke to Tripathi to learn more about the research he has done at the Rawlings lab with Treg cells. He gave an overview of the development of engineered Treg cells and their advantages over natural Treg cells.

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