Patient-specific melanoma tumor-associated antigens and neoantigens (Melanoma TAAs/Neoantigens)

Patient-specific melanoma tumor-associated antigens (TAAs) and neoantigens represent a diverse class of peptides derived from proteins expressed by melanoma cells and presented on the cell surface by Human Leukocyte Antigen (HLA) Class I and II molecules (Nature Reviews Cancer, 2017, PMID: 28912574). TAAs are self-antigens that are abnormally expressed or overexpressed in tumors, such as MAGE-A3 or tyrosinase, while neoantigens arise from non-synonymous somatic mutations unique to an individual's tumor, making them highly specific targets for the immune system (Frontiers in Immunology, 2020, DOI: 10.3389/fimmu.2020.01562). These peptide-HLA complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells and CD4+ helper T cells, triggering a targeted immune response against the malignancy. In the context of melanoma, which often has a high mutational burden, these antigens are central to the development of personalized cancer vaccines and adoptive cell therapies. Therapeutic strategies, such as mRNA-based vaccines like mRNA-4157 (V940) and tumor-infiltrating lymphocyte (TIL) therapies like Lifileucel, aim to expand and activate the patient's own T cells to recognize these specific signatures (The Lancet, 2024, PMID: 38246194; FDA, 2024). The primary challenge in targeting these antigens lies in the heterogeneity of tumor expression and the potential for immune evasion through the downregulation of HLA molecules or the development of an immunosuppressive tumor microenvironment (Journal of Clinical Investigation, 2019, PMID: 30640175).

Other names

Tumor-specific antigensTSAsNeoepitopesMelanoma-associated antigensTumor-associated antigensTAAsPeptide-MHC complexesPeptide-HLA complexes

Induction of antigen-specific CD4+ and CD8+ T-cell responses to recognize and eliminate tumor cells expressing specific peptide-HLA complexes.