CAR-T cell immunotherapy of malignant melanoma

INTRODUCTION: Management of inoperable and advanced malignant melanoma has been transformed in recent years by the advent of a number of approaches, including immune checkpoint blockade, small-molecule inhibitors, and adoptive immunotherapy with ex vivo expanded tumor-infiltrating lymphocytes. AREAS COVERED: In this review, we describe efforts made to develop an alternative immunotherapeutic approach for this disease using chimeric antigen receptor (CAR) engineered T-cells. Literature was reviewed in the PubMed database and clinicaltrials.gov website (1998-2025). EXPERT OPINION: CAR T-cell immunotherapy has proven transformative in the treatment of selected hematological malignancies. However, solid tumors such as melanoma remain much more challenging to treat using this emerging modality. Here we consider issues surrounding target selection, encompassing both tumor cells and accompanying stroma, in addition to armoring approaches that may potentiate delivery to or efficacy within the tumor microenvironment. We also consider a number of advanced CAR-based architectures to enable multi-antigen or universal antigen targeting and combination-based approaches.