Patient-specific tumor-associated and neoantigenic peptide–MHC complex (pMHC)

Patient-specific tumor-associated and neoantigenic peptide–MHC complexes are the fundamental molecular targets for advanced cancer immunotherapies, including tumor-infiltrating lymphocyte (TIL) therapy and T-cell receptor (TCR) engineered T-cell therapy [1, 15]. These complexes consist of a short peptide fragment—derived from either a tumor-specific somatic mutation (neoantigen) or an abnormally expressed protein (tumor-associated antigen)—presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, also known as Human Leukocyte Antigens (HLA) in humans [3, 18]. Because neoantigens arise from mutations unique to an individual's tumor, these complexes are recognized as non-self by the immune system, allowing for highly precise targeting that bypasses central thymic tolerance and minimizes the risk of autoimmune damage to healthy tissues [1, 19]. The recognition of these complexes by specific T-cell receptors (TCRs) triggers the activation of cytotoxic T lymphocytes, leading to the targeted destruction of malignant cells [10, 21]. Current therapeutic strategies focusing on these targets include the adoptive transfer of ex vivo expanded autologous TILs, such as the FDA-approved lifileucel, and the development of personalized neoantigen vaccines designed to elicit or amplify a patient's endogenous T-cell response against their specific tumor profile [6, 17].

Other names

Neoantigen-MHC complexTumor-specific antigen-MHC complexTSA-MHCNeoepitope-HLA complexMutant peptide-MHC complexTumor-associated antigen-MHC complex

T-cell receptor (TCR) mediated recognition and binding to the specific peptide-MHC complex on the tumor cell surface, which triggers cytotoxic T-lymphocyte activation, cytokine release, and subsequent tumor cell lysis.