Tumor-specific neoantigen-MHC complex (NeoAg-MHC) (NeoAg-MHC)

Tumor-specific neoantigens are novel peptides derived from somatic mutations in cancer cells that are not present in normal tissues (Schumacher & Schreiber, 2015). These peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, making them ideal targets for the immune system (Blass & Ott, 2021). Because they are unique to the tumor, therapies targeting these complexes—such as personalized mRNA vaccines, T-cell receptor (TCR) engineered cells, and neoantigen-specific antibodies—aim to induce a highly specific anti-tumor immune response while minimizing damage to healthy cells (Sahin & Türeci, 2018). The identification of these targets typically involves genomic sequencing and bioinformatic prediction of peptide-MHC binding affinity (Yadav et al., 2014). Current clinical efforts focus on using these complexes to drive personalized immunotherapy in various solid tumors (Ott et al., 2017).

Other names

Tumor-specific neoantigenNeoepitope-MHC complexMutation-derived antigenTSA-MHC complexNeoantigen-HLA complex

Therapeutic agents targeting neoantigen-MHC complexes primarily function by enhancing the visibility of tumor-specific mutations to the adaptive immune system. Vaccines (mRNA, DNA, or peptide) deliver the neoantigen sequence to antigen-presenting cells, which then present the neoepitope on MHC molecules to prime and expand naive T cells (Sahin & Türeci, 2018). Alternatively, adoptive cell therapies utilize T cells engineered with high-affinity T-cell receptors (TCRs) specifically designed to recognize the neoantigen-MHC complex, leading to direct cytotoxic killing of the tumor cell (Blass & Ott, 2021).