Current Aspects of Cellular Immunotherapy for Melanoma

Abstract

Melanoma is one of the most aggressive and therapy-resistant cancers, characterized by a high metastatic potential and a steadily increasing incidence. This review analyzes current approaches to cellular immunotherapy for melanoma, including tumor-infiltrating lymphocyte (TIL) therapy, TCR- and CAR-T-cell technologies, the use of NK cells, NKT cells, B cells, dendritic cells, macrophages, and immune checkpoint inhibitors. TIL therapy and PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors have demonstrated the greatest clinical efficacy, improving overall and progression-free survival in a subset of patients with advanced melanoma. TCR- and CAR-T-cell approaches have high potential due to their specific recognition of tumor antigens; however, their use is limited by toxicity, poor infiltration of solid tumors, and the difficulty of target selection. NK- and NKT-cell therapies have favorable safety profiles but require further optimization to increase antitumor activity and cell persistence in vivo. B-cell- and dendritic-cell-based vaccine strategies can induce antigen-specific immune responses and are considered promising adjuvant treatments. The development of CAR-macrophages is a new direction in cellular therapy for solid tumors. An analysis of clinical trial data shows that combination approaches that combine cellular therapy with immune checkpoint inhibitors or standard treatments are the most effective. Despite progress, the issues of toxicity, durability of the antitumor response, and overcoming the immunosuppressive tumor microenvironment remain unresolved, highlighting the need for further research in personalized immunotherapy for melanoma.