Dr Dahiya on the Unique Mechanism of Action of KITE-363 in LBCL

"We think that by dual targeting [CD19 and CD20 with KITE-363], we can decrease the antigen escape phenomena and increase immunologic pressure on the lymphoma."

Saurabh Dahiya, MD, FACP, an associate professor of medicine at Stanford University School of Medicine, as well as clinical director of Cancer Cell Therapy in the Division of Blood and Marrow Transplantation and Cell Therapy at Stanford Health Care, detailed the unique mechanism of action of KITE-363 compared with other CAR T-cell therapies for patients with relapsed/refractory large B-cell lymphoma (LBCL).

KITE-363 is distinguished as a dual-targeting bicistronic CAR T-cell therapy. It is directed against both the CD19 and CD20 antigens.

The design of KITE-363 is intended to overcome antigen escape, which is considered a major limitation associated with current CAR T-cell therapies. By implementing dual targeting, the intent is to increase the overall immunologic pressure exerted on the lymphoma.

Dahiya further explained the unique structural components related to costimulation. The CAR T-cell itself incorporates two separate costimulatory domains. Specifically, the CD20-directed CAR uses 4-1BB, while the CD19-directed CAR uses CD28. This bicistronic design confers a distinct behavioral characteristic to the CAR T cell in terms of its effector function and expansion kinetics. Dahiya noted that the application of these two different costimulatory molecules may allow for improvements in both the toxicity and the efficacy observed during the treatment of patients with relapsed/refractory LBCL.

KITE-363 was evaluated in a phase 1 trial (NCT04989803) specifically designed for patients with relapsed/refractory LBCL. Findings emerging from the study suggest that the dual-targeting approach utilized by KITE-363 has the potential to overcome antigen escape. Additionally, the therapy demonstrated strong response rates and a manageable toxicity profile, which are consistent with results seen with other currently available CAR T-cell products.