video: City of Hope's Drs. Larry Kwak and Hong Qin discuss their research on BAFF-R CAR T therapy for leukemias and lymphomas. This material relates to a paper that appeared in the Sept. 25, 2019, issue of Science Translational Medicine, published by AAAS. The paper, by H. Qin at Beckman Research Institute of City of Hope in Duarte, CA; and colleagues was titled, "CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies." view more
Credit: City of Hope
A research team has created CAR T cells that target an alternative B cell-specific surface marker, allowing them to effectively kill blood cancer cells that lack the prototypical target for CAR T therapy, CD19. The new T cells could help clinicians avoid the relapses that can occur in patients whose lymphoma cells lose CD19 - a prominent roadblock in standard CAR T cell therapy for B cell malignancies. CAR T cells are a highly effective therapy for blood cancers that have become resistant to standard treatments. However, up to 30% of patients with B cell malignancies such as lymphoma relapse after CAR T cell treatment, partly because their lymphoma cells stop expressing the target antigen. Seeking an alternative approach, Hong Qin and colleagues engineered CAR T cells that target a protein named BAFF-R, whose expression is also restricted to healthy and cancerous B cells. They tested their BAFF-R-directed CAR T cells in mice with human lymphoma cells, and found the treatment led to complete tumor regression and 100% long-term survival in the animals. The authors saw that the BAFF-R-directed CAR T cells could effectively target CRISPR-modified human leukemia cells that lacked CD19. Furthermore, the BAFF-R-CAR T cells also killed CD19-negative tumor cells isolated from four patients with leukemia who relapsed after being treated with a CD19-targeting antibody, and extended survival in mice that were implanted with cells from a fifth relapsed patient. The results show that BAFF-R is a viable target for CAR T cell treatments, although more experiments will be needed to confirm whether tumor cells could potentially evolve resistance by losing BAFF-R.
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Journal
Science Translational Medicine