Abstract 3923: Identification of membrane-expressed CAPRIN-1 as a novel and universal cancer target and generation of a therapeutic anti-CAPRIN-1 antibody TRK-950

Specific targets for cancer treatment are highly desirable, but still remain to be discovered. While previous reports suggested that CAPRIN-1 localizes in the cytoplasm, here we now show that part of this molecule is strongly expressed on the cell membrane surface in most solid cancers, but not normal tissues. Notably, the membrane expression of CAPRIN-1 extended to the subset of highly tumorigenic cancer stem cells and EMT induced metastatic cancer cells. In addition, we revealed that cancer cells with particularly high CAPRIN-1 surface expression exhibited enhanced tumorigenicity. We generated a therapeutic humanized anti-CAPRIN-1 antibody (TRK-950), which strongly and specifically binds to various cancer cells and shows anti-tumor effects via engagement of immune cells. TRK-950 was further developed as a new cancer drug and a series of pre-clinical studies demonstrates its therapeutic potency in a tumor bearing mouse model and safety in a relevant cynomolgus monkey model. Together our data demonstrate that CAPRIN-1 is a novel and universal target for cancer therapies. A phase I clinical study of TRK-950 (NCT02990481) has been completed and a phase Ib study (combination with approved drugs) is currently underway (NCT03872947). Citation Format: Fumiyoshi Okano, Takanori Saito, Yoshitaka Minamida, Shinichi Kobayashi, Takayoshi Ido, Yasushi Miyauchi, Ukei Wasai, Jiang Ke, Alexandra Aicher, Christopher Heeschen, Tetsu Yonehara. Identification of membrane-expressed CAPRIN-1 as a novel and universal cancer target and generation of a therapeutic anti-CAPRIN-1 antibody TRK-950. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3923.