Patient-specific tumor-associated antigens and neoantigen peptide-MHC complexes (Neoantigen-pMHC)

Patient-specific tumor-associated antigens and neoantigen peptide-MHC (pMHC) complexes are unique molecular signatures presented on the surface of malignant cells. These complexes consist of short peptide fragments—derived from somatic mutations (neoantigens) or abnormally expressed proteins (TAAs)—bound to Major Histocompatibility Complex (MHC) molecules (Schumacher & Schreiber, Science, 2015). Because neoantigens are products of tumor-specific genetic alterations, they are absent in healthy tissues, providing a highly specific target for the immune system while bypassing central tolerance (Sahin et al., Nature, 2017). Therapeutic interventions targeting these complexes include personalized vaccines (mRNA, DNA, or peptide-based) and adoptive T-cell therapies, such as TCR-engineered T cells (TCR-T), which are designed to recognize the specific pMHC architecture (Blass & Ott, Nature Reviews Clinical Oncology, 2021). The clinical utility of these targets is heavily dependent on the patient's HLA genotype and the tumor's mutational landscape, necessitating advanced genomic sequencing and bioinformatic prediction tools for identification (Ott et al., Nature, 2017). By facilitating the formation of an immunological synapse between the tumor cell and cytotoxic T lymphocytes, these targets enable precise, immune-mediated tumor destruction.

Other names

Neoantigen-MHC complexesTumor-specific antigens (TSA)pHLA complexesTumor-associated antigens (TAA)MHC-peptide complexesPersonalized tumor antigens

Activation of the adaptive immune system to recognize and eliminate tumor cells through the interaction of T-cell receptors with specific peptide-MHC complexes.