Topical clinical trials of targeted CAR-T therapy for solid tumors

Despite significant advancements in the treatment of hematological neoplasms, the use of CAR-T cell therapy for solid tumors, especially ovarian cancer, faces a number of significant challenges: tumor heterogeneity, the antigen escape phenomenon, an extremely immunosuppressive tumor microenvironment and frequent resistance to platinum-based drugs. In order to overcome these obstacles, innovative strategies are being actively developed, including multi-targeted CAR-T cells, advanced CAR designs targeting specific antigens, combined treatments with immune checkpoint inhibitors (such as cemiplimab) and anti-angiogenesis agents (such as bevacizumab), as well as lymphodepleting chemotherapy and different routes of administration for CAR-Ts (intravenous, intraperitoneal, intrapleural). Current clinical trials (NCT07067255 - NCT04981119) are actively investigating the safety and efficacy of CAR-T cell therapy targeting various antigens, such as MUC16 (CA-125), mesothelin (MSLN), CD146, GPC3, FSHR, B7-H3, CLDN6, HLA-G, and others. These studies demonstrate progress in overcoming barriers to CAR-T therapy for ovarian cancer and offer new prospects for patients with recurrent and refractory ovarian tumors.