Bispecific PSMA antibodies and CAR-T in metastatic castration-resistant prostate cancer

作者：Kevin Kayvan Zarrabi, Vivek Narayan, Patrick Johnston Mille, Matthew R. Zibelman, Benjamin Miron, Babar Bashir, William Kevin Kelly · 发表于：Therapeutic Advances in Urology · 年份：2023 · DOI：10.1177/17562872231182219 · 被引用次数：45 · 研究领域：CAR-T cell therapy research、Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers

Prostate cancer is the most common cancer among men and the second leading cause of cancer-related deaths in men in the United States. The treatment paradigm for prostate cancer has evolved with the emergence of a variety of novel therapies which have improved survival; however, treatment-related toxicities are abundant and durable responses remain rare. Immune checkpoint inhibitors have shown modest activity in a small subset of patients with prostate cancer and have not had an impact on most men with advanced disease. The discovery of prostate-specific membrane antigen (PSMA) and the understanding of its specificity to prostate cancer has identified it as an ideal tumor-associated antigen and has revived the enthusiasm for immunotherapeutics in prostate cancer. T-cell immunotherapy in the form of bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cell therapy have shown exceptional success in treating various hematologic malignancies, and are now being tested in patients with prostate cancer with drug design centered on various target ligands including not just PSMA, but others as well including six-transmembrane epithelial antigen of the prostate 1 (STEAP1) and prostate stem cell antigen (PSCA). This summative review will focus on the data surrounding PSMA-targeting T-cell therapies. Early clinical studies with both classes of T-cell redirecting therapies have demonstrated antitumor activity; however, there are multiple challenges with this class of a...