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Dr. Powell and colleagues have developed MISIIR-specific CAR T cells with distinct single-chain antibody variable fragments of MISIIR, coupled to CD27 and CD3z intracellular signaling domains. The select GM7-27Z CAR variant exhibits antigen-specific reactivity, cytokine secretion and tumor cell lysis in vitro against a broad range of human tumor cell lines including ovarian and endometrial cancer expressing variable levels of endogenous MISIIR. GM7-27Z does not exhibit cytotoxicity when co-cultured with a broad panel of normal primary human cells, suggesting a safe profile of targeting. Additionally, in vivo GM7 CAR T cells showed potent antitumor effect in immunocompromised mice bearing large established subcutaneous C30.
MISIIR tumors, completely clearing 60% of the tumors and significantly prolonging mice survival. Overall, the GM7-27Z variant supports the potential of MISIIR as a novel target for the efficacious and safe treatment of ovarian cancer and other gynecologic malignancies using CAR T cell therapy.