SUMMARY: UCLA researchers in the Department of Microbiology, Immunology and Molecular Genetics have developed a novel platform to generate potent, high quality Vδ2 T cells at scale for use in cancer immunotherapies.
BACKGROUND: With rising cases of cancer in the world, immunotherapies have emerged as a promising and potentially effective therapeutic strategy. In particular, chimeric antigen receptor-T (CAR-T) cell therapy makes use of reengineered T-cells to target and clear cancer cells. Conventional CAR-T cell therapy begins by collecting T-cells from patients; then, in a laboratory setting, the cells are genetically modified to express a CAR molecule on their surface. A large population of these designer cells are then reintroduced back into the patient where they attack and kill cancer cells expressing the target molecule of the CAR. However, one of the major limitations of current engineered T cell therapies is the requirement of autologous T cells as the cellular vehicle to prevent potential tissue damage from alloreactivity of donor T cells to HLA-mismatched recipients. While CAR-T cell therapy has been successful for the treatment of blood cancers, it is less effective on solid tumors. Thus, there is a strong need for improved and safe immunotherapies for other cancer types. Vδ2 T cells, a common subset of gamma delta (γδ) T cells, are attractive because they do not cause graft-versus-host disease and possess intrinsic cancer killing abilities. Their clinical application for cancer immunotherapy, however, is limited by their scarcity and persistence, as well as tumor immunosuppression mechanisms. Novel platforms to enhance the clinical utility of Vδ2 could transform cancer treatments.
INNOVATION: Researchers at UCLA led by Dr. Lili Yang in the Department of Microbiology, Immunology and Molecular Genetics have developed a γδ T cell platform to overcome challenges of scarcity and tumor suppression efficiency of typical endogenous cells. The platform consists of a screening process for CD16 expression to select cells with robust cytotoxicity activity and optimized cell expansion methods to increase rates up to 4000-fold while maintaining optimal cellular phenotype. With this T cell platform, one can produce active and allogeneic Vδ2 T cells at large scale for applications in cancer immunotherapies.
POTENTIAL APPLICATIONS: • CAR-T cell expansion and screening platform for cancer therapeutics
ADVANTAGES: • Increased safety with allogeneic T cells • Larger scalability and tumor suppression efficiency compared to conventional gamma delta (γδ) T cells
DEVELOPMENT-TO-DATE: Proof of concept shown in human in vitro cells
Related Papers (from the inventors only): Li, Y. R., Dunn, Z. S., Yu, Y., Li, M., Wang, P., & Yang, L. (2023). Advancing cell-based cancer immunotherapy through stem cell engineering. Cell stem cell, S1934-5909(23)00070-X. Advance online publication. https://doi.org/10.1016/j.stem.2023.02.009