Patient-specific tumor neoantigen–MHC–TCR complex (NeoAg-MHC-TCR complex)

The patient-specific tumor neoantigen–MHC–TCR complex is a tripartite molecular interaction fundamental to the adaptive immune system's ability to recognize and eliminate cancer cells. Neoantigens are novel peptides derived from non-synonymous somatic mutations unique to an individual's tumor, which are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, also known as Human Leukocyte Antigens (HLA) in humans [1, 4]. These peptide-MHC (pMHC) complexes are subsequently recognized by highly specific T-cell receptors (TCRs), initiating a targeted cytotoxic response [1, 13]. Because neoantigens are absent from normal tissues, they serve as ideal, highly specific therapeutic targets that minimize the risk of central tolerance and autoimmune reactivity [6, 12]. In modern oncology, this complex is the primary target for several personalized immunotherapy modalities, including neoantigen vaccines (e.g., mRNA-4157) and adoptive T-cell receptor-engineered T-cell (TCR-T) therapies [3, 15]. Vaccines aim to prime and expand the patient's endogenous T-cell repertoire to recognize these complexes, while TCR-T therapy involves engineering a patient's own T cells to express a TCR with high affinity for a specific neoantigen-MHC pair [7, 10]. Despite their high specificity, challenges remain, such as the potential for tumor immune escape through the downregulation of MHC expression and the technical complexity of identifying truly immunogenic neoantigens from a patient's mutational profile [1, 3, 12].

Other names

Neoantigen-HLA-TCR complexTumor-specific antigen-MHC-TCR complexpMHC-TCR complexNeoepitope-MHC-TCR complexPersonalized neoantigen-MHC-TCR complex

T-cell receptor-mediated recognition of a specific mutated peptide (neoantigen) presented by Major Histocompatibility Complex (MHC) molecules on the tumor cell surface, which triggers T-cell activation, secretion of cytotoxic granules (perforin and granzymes), and targeted lysis of the cancer cell.