Peptide-Human Leukocyte Antigen class I complexes (HPV16 E7, MAGEC2, MAGEA4, PRAME, MAGEA1) (pMHC complexes)

Peptide-Human Leukocyte Antigen (HLA) class I complexes (pMHC) are the primary targets for T-cell-based immunotherapies, where intracellular proteins are degraded into short peptides and presented on the cell surface by HLA molecules [1, 4]. The specific antigens in this group—HPV16 E7 (a viral oncogene), and MAGEC2, MAGEA4, PRAME, and MAGEA1 (Cancer-Testis Antigens)—are highly expressed in various solid and hematological malignancies but have restricted expression in healthy adult tissues, making them ideal for targeted therapy [6, 9, 15]. Because these antigens are located inside the cell, they are inaccessible to traditional monoclonal antibodies; however, the pMHC complex can be recognized by engineered T-cell receptors (TCRs) or TCR-mimic (TCRm) antibodies [1, 12]. Therapeutic modalities such as TCR-engineered T cells (TCR-T) and TCR-bispecific engagers (TCERs) have shown significant clinical activity in cancers like synovial sarcoma and HPV-associated epithelial cancers [3, 11]. The effectiveness of these therapies is strictly limited by the patient's HLA genotype (HLA restriction) and the risk of off-target toxicity if the therapeutic agent cross-reacts with similar peptides in normal tissues [2, 6, 8].

Other names

pMHC complexesPeptide-MHC class I complexesHLA-peptide complexesMHC-restricted antigensTumor-associated antigen peptide-HLA complexes

T-cell receptor binding and redirected T-cell cytotoxicity