MRNA-BASED VACCINES IN MELANOMA THERAPY: MECHANISMS, ADVANCES, AND CLINICAL PERSPECTIVES

Melanoma is an aggressive type of skin cancer that has high metastatic ability and resists standard therapies such as radiotherapy, chemotherapy, and targeted therapy. Although, signific ant advancements have been achieved in the evolving field of immunotherapy especially immune checkpoint inhibitors; several hurdles including heterogeneous response and treatment resistance are still challenging for chronic diseases. In this context, mRNA-based vaccines represent an innovative and promising approach to melanoma therapy. Herein, we review how melanomagenesis is understood at the biological level including origins (and genetic mutations: BRAF, NRAS); tumor microenvironment; and mechanisms of immune evasion. It also focuses more on the principles of mRNA vaccine technology, including types of vaccines and structural components and delivery systems (lipid nanoparticles, etc. This includes an overview of the mechanism of action of mRNA vaccines and their ability to mount robust cellular and humoral immune responses by presentation of antigens with T-cell activation. The review also discusses melanoma mRNA vaccines including tumor-associated antigens and personalized neoantigens. Considering clinical advances, innovative approaches like early-phase trial designs and combinations with immune checkpoint inhibitors are discussed for their promising safety effective potential. The report covers advantages of mRNA vaccines, e.g., fast production, specificity to the antigen and personalization potential; it also addresses major challenges such as stability/delivery efficiency/cost. Future directions will ultimately emphasize the promise of AI/augmented delivery systems, and wider applications across a number of cancers. Ultimately, mRNA vaccines represent a groundbreaking strategy for melanoma treatment with remarkable capacity to improve therapeutic results for patients and reshape oncology immunotherapeutics.