Recent Advances and Challenges in Uveal Melanoma Immunotherapy

SIMPLE SUMMARY: Uveal melanoma is the most common primary intraocular malignancy in adults. Although it can be controlled locally, half of the patients still develop metastases. To date, there have been no standard therapeutic strategies for the prevention or treatment of metastases. Existing therapies, such as chemotherapy and targeted therapies, induce only minimal responses. This review focuses on newly published research on immunotherapy. We highlight expanding treatments and their clinical outcomes, as well as propose promising new treatments and feasible checkpoints. Based on these findings, we provide innovative insights into feasible strategies for the treatment of patients with uveal melanoma. ABSTRACT: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Compared to cutaneous melanoma (CM), which mainly harbors BRAF or NRAS mutations, UM predominantly harbors GNAQ or GNA11 mutations. Although primary UM can be controlled locally, approximately 50% of patients still develop metastases. To date, there have been no standard therapeutic strategies for the prevention or treatment of metastases. Unfortunately, chemotherapy and targeted therapies only induce minimal responses in patients with metastatic UM, with a median survival time of only 4–5 months after metastasis detection. Immunotherapy agents, such as immune checkpoint inhibitors, have achieved pioneering outcomes in CM but have shown limited effects in UM. Researchers have explored several feasible checkpoints to identify options for future therapies. Cancer vaccines have shown little in the way of therapeutic benefit in patients with UM, and there are few ongoing trials providing favorable evidence, but adoptive cell transfer-related therapies seem promising and deserve further investigation. More recently, the immune-mobilizing monoclonal T-cell receptor against the cancer molecule tebentafusp showed impressive antitumor effects. Meanwhile, oncolytic viruses and small molecule inhibitors have also gained ground. This review highlights recent progress in burgeoning treatments and provides innovative insights on feasible strategies for the treatment of UM.