Tumor neoantigen peptide–MHC complex (pMHC)

The tumor neoantigen peptide–MHC complex is a highly specific therapeutic target formed by the presentation of mutated protein fragments, unique to cancer cells, on the cell surface via Major Histocompatibility Complex (MHC) molecules. These neoantigens arise from somatic mutations, such as point mutations or frameshifts, and are absent in healthy tissues, providing a clear distinction for the immune system to recognize malignant cells. Recognition of these complexes by T cell receptors (TCRs) is the fundamental step in the adaptive immune response against tumors, triggering T cell activation and subsequent tumor cell lysis. Therapeutic strategies targeting these complexes include neoantigen-specific TCR-engineered T cell (TCR-T) therapies, which endow T cells with high-affinity receptors for a specific pMHC, and neoantigen vaccines designed to stimulate the patient's own endogenous T cell repertoire. While these therapies offer the potential for high precision and reduced autoimmunity compared to traditional treatments, they are limited by the requirement for patient-specific HLA matching and the risk of tumor escape through the loss of MHC expression or antigen presentation. Current clinical development focuses on both personalized approaches and off-the-shelf TCRs targeting shared neoantigens like those found in KRAS or TP53 mutations.

Other names

Neoantigen-MHC complexNeoepitope-MHC complexTumor-specific antigen-MHC complexpMHC complexMutation-derived peptide-MHC complex

Recognition by engineered or endogenous T cells leading to targeted cytotoxicity, cytokine release, and tumor cell lysis.