Tumor antigen peptide–MHC complex (pMHC (when referring to the peptide–MHC complex), or tumor antigen pMHC complex for specificity)

A tumor antigen peptide–MHC complex is a cell surface molecular complex in which a fragment of a tumor-associated or tumor-specific protein (antigenic peptide) is presented by a major histocompatibility complex (MHC) molecule (either MHC class I or class II). This complex is specifically recognized by T-cell receptors (TCRs), including those that have been introduced or engineered for cancer immunotherapy[1][2][3][4][5][6][7]. The high specificity of TCRs for both the presenting MHC allele and the bound peptide forms the molecular basis for targeted immunotherapies, allowing genetic, structural, or synthetic engineering of TCRs to direct T cells to recognize and kill tumor cells while mostly sparing healthy cells. The diversity and polymorphism of MHC alleles, together with the sequence of the presented peptide, confer selectivity and define therapeutic scope and safety profiles[4][6][7]. Engineered TCR therapies utilize this platform to redirect immune attack toward tumors displaying these complexes, but cross-reactivity with healthy tissue and unintended immune activation remain significant concerns[7]. According to current structural and therapeutic literature, off-target reactivity to healthy tissue is a well-documented safety concern for TCR-based therapies, underscoring the need for careful design and screening[7].

Other names

Tumor-associated peptide–major histocompatibility complex complexTumor peptide–MHC complexTumor antigen pMHCCancer antigen peptide–MHC complex

Recognition by engineered or introduced T-cell receptor enables selective targeting and killing of cells displaying the specific peptide–MHC (pMHC) complex Immune activation leading to cytotoxic T cell-mediated lysis of tumor cells