Tumor-associated and neoantigen peptide–Major Histocompatibility Complex class I (pMHC-I) (pMHC-I)

Tumor-associated and neoantigen peptide–Major Histocompatibility Complex class I (pMHC-I) complexes are the fundamental units of recognition for the adaptive cellular immune system, presenting the internal proteome of a cell to the surface for surveillance by CD8+ T-cells (Source: Nature Reviews Cancer, 2021). These complexes are formed when intracellular proteins are processed into short peptides and loaded onto MHC class I molecules, which in humans are known as Human Leukocyte Antigens (HLA) (Source: NIH/NCI). In malignant cells, these peptides may be derived from mutated proteins (neoantigens), overexpressed proteins (tumor-associated antigens), or cancer-testis antigens, providing a specific signature for immune targeting (Source: PubMed, 2020). Therapeutic strategies such as TCR-engineered T-cells (TCR-T) and bispecific TCR-based engagers are designed to bind these specific pMHC-I complexes with high affinity, bypassing the limitations of natural T-cell immunity (Source: FDA, 2024). This approach allows for the targeting of intracellular oncogenic drivers, such as MAGE-A4 or NY-ESO-1, which are not accessible to traditional antibody-based therapies (Source: Journal for ImmunoTherapy of Cancer, 2020). However, the efficacy of these therapies is contingent upon the patient's HLA genotype and the consistent expression of the target complex, while safety remains a concern due to potential cross-reactivity with similar peptides in healthy tissues (Source: FDA Label, Kimmtrak).

Other names

pMHC complexpHLA complexHLA-peptide complexTumor-specific antigen-MHC complexMHC-I restricted antigenAntigen-presenting complex

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-mimetic antibodies to induce T-cell mediated lysis of the tumor cell.