Peptide-Major Histocompatibility Complex presenting lung cancer-associated antigens (pMHC)

Peptide-Major Histocompatibility Complex (pMHC) complexes presenting lung cancer-associated intracellular tumor antigens are pivotal structures for the immune recognition of malignant cells (Nature Communications, 2020, 11:1). These complexes are formed when intracellular proteins, such as cancer-testis antigens (e.g., MAGE-A4, NY-ESO-1) or neoantigens, are degraded by the proteasome and the resulting peptides are loaded onto MHC Class I molecules for surface display (Journal of Hematology & Oncology, 2021, 14:1). In lung cancer, these pMHCs provide a unique window into the cell's internal proteome, allowing the immune system to identify cells expressing oncogenic or aberrant proteins. Therapeutic interventions, particularly TCR-engineered T-cell (TCR-T) therapies like afamitresgene autoleucel, are designed to recognize these specific pMHC targets with high affinity (Adaptimmune Therapeutics, 2024). By bypassing the need for surface-expressed proteins, pMHC-targeted therapies significantly expand the landscape of targetable molecules in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, the efficacy of these treatments can be limited by the heterogeneity of antigen expression and the potential for off-target toxicity if the peptide is also presented at low levels in vital healthy tissues (Immatics N.V., 2023).

Other names

pMHC complexHLA-peptide complexTumor antigen-MHC complexMHC-restricted tumor antigenNeoantigen-HLA complex

Binding of engineered T-cell receptors (TCRs) or TCR-like antibodies to the specific peptide-MHC complex, leading to T-cell activation and targeted lysis of the tumor cell.