TCR-Directed Therapy in the Treatment of Metastatic Uveal Melanoma

SIMPLE SUMMARY: Technical advances in immunotherapies have led to the development of novel T cell receptor (TCR)-based approaches to fight cancer. One of these therapies, tebentafusp, has shown a significant benefit in the overall survival of uveal melanoma patients for the first time. This review focuses on TCR-directed therapies in the treatment of uveal melanoma. ABSTRACT: Metastatic uveal melanoma (mUM) is one of the most rapidly progressing tumors, with a bad prognosis and no standard-of-care treatment. Immune checkpoint inhibitors have revolutionized cancer therapy and improved overall survival in patients with metastatic cutaneous melanoma (mCM). However, this approach has been largely unimpressive, with no significant impact on the survival of mUM patients. Technical advances in immunotherapies have led to the development of novel T cell receptor (TCR)-based approaches to fight cancer. For the first time in over 50 years, compelling evidence demonstrates the power of TCR-based approaches for survival in mUM patients. Hence, this review summarizes novel TCR-based immunotherapeutic strategies currently in clinical studies for mUM treatment. We also discuss the potential combinational treatments to these strategies to maximize the clinical benefits.