Optimization of immunotherapy through therapeutic vaccines in cutaneous melanoma: a review of clinical trials

Cutaneous melanoma is responsible for approximately 80% of skin cancer-related mortality. While immunotherapy has significantly improved disease management, recurrence remains frequent due to the progressive loss of immune responsiveness. Immunomodulatory vaccines offer a potential strategy to restore antitumor immunity; however, their diverse formulations and mechanisms of action pose challenges in identifying the most effective approach. This review included clinical trials of immunomodulatory vaccines in patients with cutaneous melanoma available in PubMed, conducted between January 2015 and March 2024. A total of 34 clinical trials were analyzed: 64.7% were phase II, 29.4% were phase I, and 5.9% were phase III. The mean follow-up duration was 47 ± 41.2 months. Phase I studies demonstrated the potential of vaccines such as UV1 and GEN0101 to induce tumor regression and antigen-specific immune responses. Phase II trials of peptide- and dendritic cell-based vaccines showed improvements in both overall and disease-free survival. Phase III results, however, were inconclusive. No severe adverse events attributable to vaccination were reported. Immunomodulatory vaccines, particularly when integrated with genotypic and phenotypic profiling, represent a promising therapeutic option for cutaneous melanoma. Nevertheless, confirmation of their efficacy requires further evaluation in adequately powered phase III trials.