Human leukocyte antigen A2-restricted tumor-associated antigen peptide (HLA-A2-restricted TAA peptide)

HLA-A2-restricted tumor-associated antigen (TAA) peptides are short amino acid sequences, typically 9 to 11 residues in length, that are derived from the degradation of intracellular proteins and presented on the cell surface by the Human Leukocyte Antigen A*02:01 molecule (PubMed: 31434690). HLA-A2 is the most common MHC class I allele in many populations, making it a primary focus for the development of T-cell receptor (TCR)-based immunotherapies (NIH: PMC7066453). These peptides represent a diverse array of targets, including cancer-testis antigens (e.g., NY-ESO-1, MAGE-A4), lineage-specific antigens (e.g., gp100, MART-1), and overexpressed proteins (e.g., PRAME, WT1) (Nature Reviews Cancer: 10.1038/s41568-021-00346-0). Unlike traditional antibody targets which must be surface-expressed, these peptide-MHC complexes allow the immune system to survey the internal proteome of the cell. Therapeutic agents such as TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers (e.g., Tebentafusp) are designed to recognize these specific complexes with high affinity, leading to the targeted destruction of tumor cells (NEJM: 10.1056/NEJMoa2103481). However, the use of these targets requires patients to possess the specific HLA-A*02:01 genotype and for the tumor to maintain expression of both the antigen and the HLA molecule (The Lancet: 10.1016/S0140-6736(24)00319-2).

Other names

HLA-A*02 restricted peptidesMHC class I-restricted tumor antigensHLA-A2-presented TAA peptidespMHC complexesHLA-A2-restricted tumor antigens

Engagement of the peptide-HLA complex by a natural or synthetic T-cell receptor (TCR) or TCR-mimetic, triggering T-cell mediated cytotoxicity.