St. Jude Reference #SJ-13-0031
To expand applications for T cell-based immunotherapy in cancer, we designed a universal CD16V-BB-zeta chimeric receptor that augments the efficacy of antibody therapy against multiple tumors. The receptor contains a high-affinity gene variant, the hinge and transmembrane domains of CD8alpha, and the signaling domains of CD3zeta and 4-1BB. The receptor binds the Fc portion of human immunoglobulins and delivers activation signals.
This receptor specifically killed lymphoma cell lines and primary chronic lymphocytic leukemia cells in the presence of Rituximab at low effector : target ratio. The anti-HER2 antibody Trastuzumab triggered CD16V-BB-zeta-mediated antibody-dependent cell cytotoxicity against breast and gastric cancer cells, and the anti-GD2 antibody hu12.18K322A against neuroblastoma and osteosarcoma cells. A method based on electroporation of CD16V-BB-zeta mRNA was developed to facilitate clinical transition and efficient receptor expression without the use of viral vectors. (This invention is co-owned with National University of Singapore).
Our results offer preclinical proof-of-concept for CD16V-BB-ζ as a universal, next generation chimeric receptor with the potential to augment the efficacy of antibody therapies for cancer.
T Cell Therapy, CD16V-BB-zeta chimeric receptor, cancer, cell therapy, immunomodulation
Granted Patents or Published Applications
Provisional patent application available under confidentiality
Related Scientific References
Kudo K, Imai C, Lorenzini P, Kamiya T, Kono K, Davidoff AM, Chng WJ, Campana D., T Lymphocytes Expressing a CD16 Signaling Receptor Exert Antibody-Dependent Cancer Cell Killing. Cancer Res. Epub 2013 Nov 6. [Epub ahead of print]
See also comments on: Baas R., T Cells Go Universal.
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