Patient-specific neoantigen- and tumor-associated antigen-derived peptides presented on MHC on autologous tumor cells (Neoantigen/TAA-MHC complex)

Patient-specific neoantigen- and tumor-associated antigen (TAA)-derived peptides presented on the Major Histocompatibility Complex (MHC) represent a critical class of targets for personalized cancer immunotherapy (Schumacher & Schreiber, Science 2015). Neoantigens arise from non-synonymous somatic mutations unique to an individual's tumor, making them highly specific and less likely to induce central tolerance compared to TAAs, which are self-antigens overexpressed in tumors (Sahin & Türeci, Science 2018). These peptides are processed intracellularly and displayed on the cell surface by MHC class I or II molecules, where they are recognized by the T-cell receptors (TCRs) of CD8+ and CD4+ T cells, respectively (Blass & Ott, Nature Reviews Clinical Oncology 2021). Therapeutic strategies targeting these complexes include personalized mRNA or DNA vaccines, such as mRNA-4157, and adoptive cell therapies like TCR-engineered T cells (TCR-T) and tumor-infiltrating lymphocytes (TILs). By leveraging the high specificity of these antigens, these treatments aim to elicit a robust and durable anti-tumor immune response while minimizing damage to healthy tissues. However, clinical success is often challenged by the heterogeneity of antigen expression within the tumor and the ability of cancer cells to evade detection by downregulating MHC molecules or through other components of the immunosuppressive tumor microenvironment.

Other names

Tumor-specific neoantigens (TSNA)Tumor-associated antigens (TAA)Peptide-MHC complex (pMHC)NeoepitopesCancer-germline antigensTumor-specific antigens (TSA)MHC-restricted tumor antigens

Induction of antigen-specific T-cell responses through the recognition of peptide-MHC complexes by T-cell receptors (TCRs), leading to the targeted lysis of tumor cells.