Peptide–Major Histocompatibility Complex presenting tumor-associated antigens (pMHC-TAA) (pMHC-TAA)

Peptide–Major Histocompatibility Complex (pMHC) complexes presenting patient-specific tumor-associated antigens, particularly neoantigens, are central to personalized cancer immunotherapy [1, 5]. These complexes are formed when mutated or overexpressed proteins within a tumor cell are processed into short peptides and displayed on the cell surface by MHC (HLA in humans) molecules [1]. This presentation allows the immune system to distinguish malignant cells from healthy ones by recognizing unique "non-self" signatures [5]. Therapeutic approaches targeting these complexes include personalized neoantigen vaccines, such as mRNA-4157, and adoptive T-cell therapies using engineered T-cell receptors (TCRs) [2, 3]. Because these targets are often unique to an individual's tumor, they offer a high degree of specificity, potentially reducing off-target effects compared to traditional therapies [5]. However, challenges remain, including the need for complex bioinformatics to identify suitable neoantigens and the risk of tumor escape through HLA downregulation [4]. Despite these hurdles, pMHC complexes remain one of the most promising avenues for achieving durable clinical responses in oncology [3].

Other names

pMHC complexHLA-peptide complexTumor-specific antigen-MHC complexNeoantigen-MHC complexTumor-associated antigen-HLA complex

Drugs targeting pMHC-TAA complexes typically utilize engineered T-cell receptors (TCRs) or TCR-like antibodies to recognize the specific peptide-HLA combination, leading to direct T-cell mediated lysis of the tumor cell [2, 3].