Tumor-associated antigen and neoantigen peptide-Major Histocompatibility Complex (pMHC)

Tumor-associated antigens (TAAs) and mutated tumor peptides (neoantigens) presented on Major Histocompatibility Complex (MHC) molecules are critical targets for modern cancer immunotherapy. These complexes consist of short peptide fragments, derived from intracellular proteins, that are loaded onto MHC Class I or II molecules and displayed on the cell surface for surveillance by T-cells [1, 2]. TAAs include overexpressed proteins or cancer-testis antigens, while neoantigens are derived from non-synonymous somatic mutations unique to the tumor, making them highly specific targets [3, 5]. Therapeutic interventions such as TCR-engineered T-cells (TCR-T), bispecific T-cell engagers (BiTEs), and personalized cancer vaccines are designed to recognize these specific peptide-MHC (pMHC) signatures [4, 6]. By engaging the adaptive immune system, these therapies facilitate the selective destruction of malignant cells while attempting to minimize damage to healthy tissues [2, 7]. However, the effectiveness of these treatments can be limited by tumor-mediated HLA downregulation or the risk of cross-reactivity with similar peptides found in vital organs [8, 10].

Other names

Tumor-associated antigensNeoantigensTumor-specific antigensCancer-testis antigenspHMC complexesMHC-presented peptides

Recognition of specific peptide-MHC complexes by engineered T-cell receptors (TCRs) or TCR-mimetic antibodies, leading to T-cell activation, secretion of cytotoxic cytokines, and granzyme-mediated lysis of tumor cells [2, 4, 6].