Tumor-associated antigen peptide-Major Histocompatibility Complex class I (TAA-MHC I) (TAA-MHC I)

Tumor-associated antigen (TAA) peptides presented on MHC class I molecules are short protein fragments, typically 8-11 amino acids in length, derived from intracellular proteins and displayed on the surface of malignant cells. These complexes serve as the primary 'molecular signature' that allows the adaptive immune system, specifically CD8+ cytotoxic T cells, to identify and eliminate cancerous cells (Source: Janeway's Immunobiology). In the context of immunotherapy, these complexes are highly specific targets because they represent the internal proteome of the cell, including mutated neoantigens, overexpressed self-antigens, or cancer-testis antigens that are not typically found on healthy adult tissues. Therapeutic interventions such as TCR-engineered T-cell therapies (TCR-T) and bispecific T-cell engagers are designed to recognize these specific peptide-HLA combinations with high affinity. However, the effectiveness of these therapies is often limited by the requirement for specific HLA genotypes in patients and the potential for tumor cells to evade detection by downregulating their MHC expression (Source: Frontiers in Immunology, 2020).

Other names

pHLA complexPeptide-HLA class I complexTumor-specific antigen-MHC complexNeoantigen-MHC complexCancer-testis antigen-MHC complexpMHC

Drugs targeting these complexes, such as TCR-engineered T cells or bispecific T-cell engagers (ImmTACs), bind specifically to the unique interface formed by the tumor peptide and the MHC molecule. This binding triggers the recruitment and activation of cytotoxic T lymphocytes (CTLs), which release perforins and granzymes to induce apoptosis in the target tumor cell (Source: Nature Reviews Drug Discovery, 2021; FDA Label for Kimmtrak).