Tumor-associated antigen-derived peptide presented on MHC class I (TAA-MHC I)

Tumor-associated antigen-derived peptides presented on MHC class I molecules (TAA-MHC I) represent a critical class of targets for cancer immunotherapy [Source: PubMed PMID 29463741]. These targets consist of short peptide fragments, typically 8-11 amino acids in length, derived from intracellular tumor proteins that are processed by the proteasome and displayed on the cell surface by Major Histocompatibility Complex (MHC) class I molecules [Source: NIH/NCI]. Unlike traditional antibody targets that are limited to surface-expressed proteins, TAA-MHC I complexes allow the immune system to recognize the internal proteome of a cancer cell, including transcription factors and cancer-testis antigens [Source: Nature Reviews Cancer]. Therapeutic strategies targeting these complexes include TCR-engineered T cells (TCR-T), soluble bispecific TCR-based engagers, and cancer vaccines [Source: FDA/Tecelra, FDA/Kimmtrak]. The clinical success of these therapies depends on the high specificity of the recognition agent for the specific peptide-MHC combination to avoid lethal cross-reactivity with similar peptides presented on healthy tissues [Source: PubMed PMID 23644516].

Other names

pMHC complexPeptide-HLA complexTumor-specific peptide-MHCHLA-restricted tumor antigenPeptide-major histocompatibility complex

Recognition by engineered T-cell receptors (TCRs) or TCR-like bispecific molecules leading to the targeted activation of cytotoxic T lymphocytes and subsequent lysis of the tumor cell [Source: PubMed PMID 29463741].