Mrna-Based Melanoma Vaccines Targeting Gp100 and Trp2 Macromolecules Publisher



Hosseini Kakroudi M ; Rezvanimehr A ; Zolfaghari K ; Baghaeishiva G ; Abbasi H ; Pourashory M ; Yazdanpanah N ; Saleki K ; Rezaei N
Source: Discover Oncology Published:2026

Abstract

Melanoma, an aggressive form of skin cancer, is responsible for more than 80% of skin cancer mortality, despite representing only about 1% of all skin cancer cases. Against traditional treatments, a new generation of immunotherapies, including cancer vaccinations, has gained increasing attention for durable remission in advanced stages. Among them, Messenger RNA (mRNA) vaccines have arisen as a promising immunotherapy, with the ability to encode tumor-specific antigens to stimulate immune responses. In melanoma, shared melanocytic differentiation antigens such as glycoprotein 100 (gp100) and tyrosinase-related protein-2 (TRP-2) are targets due to their recurrent expression and immunogenic epitopes. In this review, we aimed to explain the mRNA vaccine design and delivery strategies with an antigen-centered focus on gp100 and TRP-2, emphasizing their design, immune interaction, preclinical and clinical utilization by classifying different types of studies. In vivo evidence demonstrated how LNP-based mRNA vaccines induce cytotoxic CD8⁺ T cell responses. mRNA vaccines have also demonstrated clinical potential in patients with melanoma; however, there are only a few clinical trials in phases I and II, where mRNA vaccines have been tested. Besides wide application of mRNA vaccines, there are Key challenges including delivery-related reactogenicity and safety considerations, especially in combination regimens. At the end of this review, we indicated computational Immunoinformatics in epitope prediction and design of immunotherapies targeting melanoma and Artificial Intelligence (AI) technologies. This review highlights the potential of mRNA vaccines in melanoma management, concentrating on ongoing improvements and future directions to address current challenges and improve therapeutic efficacy. © The Author(s) 2026.