Journal
CANCER RESEARCH COMMUNICATIONS
Volume 3, Issue 4, Pages 641-659Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2767-9764.CRC-22-0310
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CAPRIN-1, expressed on the cell membrane surface, is a promising target for cancer treatment. It is present in highly tumorigenic cancer stem cells and metastatic cancer cells induced by epithelial-mesenchymal transition (EMT). A therapeutic humanized anti-CAPRIN-1 antibody (TRK-950) has been developed and shown to bind specifically to cancer cells and exhibit antitumor effects. Clinical studies of TRK-950, including a phase I study and a phase Ib study in combination with approved drugs, are underway.
Specific targets for cancer treatment are highly desirable, but still remain be discovered. While previous reports suggested that CAPRIN-1 localizes in the cytoplasm, here we now show that part of this molecule is strongly ex-pressed 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 epithelial-mesenchymal transition (EMT)-induced metastatic cancer cells. In addition, we revealed that cancer cells with particularly high CAPRIN-1 surface expression ex-hibited enhanced tumorigenicity. We generated a therapeutic humanized anti-CAPRIN-1 antibody (TRK-950), which strongly and specifically binds to various cancer cells and shows antitumor effects via engagement of im-mune cells. TRK-950 was further developed as a new cancer drug and series of preclinical studies demonstrates its therapeutic potency in tumor bearing mouse models 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 has been completed (NCT02990481) and a phase Ib study (combination with ap- proved drugs) is currently underway (NCT03872947) in the United States and France. In parallel, a phase I study in Japan is in progress as well (NCT05423262).
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