HLA-A*24:02-restricted Alpha-fetoprotein peptide 357-365 (HLA-A*24:02/AFP357)

The HLA-A*24:02-restricted Alpha-fetoprotein (AFP) peptide 357-365 is a specific peptide-MHC complex consisting of the HLA-A*24:02 allele presenting a 9-amino acid fragment (EYILSLEEL) derived from the oncofetal protein Alpha-fetoprotein. AFP is a well-characterized tumor-associated antigen that is highly expressed during fetal development and in the majority of hepatocellular carcinoma (HCC) cases, but its expression is significantly repressed in healthy adult tissues. The HLA-A*24:02 allele is one of the most common MHC Class I alleles in East Asian populations, where the prevalence of HCC is particularly high, making this complex a high-priority target for precision immunotherapy. Therapeutic approaches targeting this complex include T-cell receptor (TCR) engineered T cells and TCR-like CAR-T cells, such as ET1402L1, which are designed to recognize the intracellularly derived peptide when displayed on the cell surface. Because AFP is a secreted protein, traditional antibody therapies are often ineffective; however, targeting the processed peptide in the context of HLA allows for the direct targeting of the malignant cells themselves. Clinical development focuses on leveraging this specificity to treat advanced HCC while minimizing damage to healthy liver tissue, although monitoring for off-tumor effects in cases of liver regeneration is a critical safety consideration.

Other names

AFP357-365/HLA-A*24:02 complexEYILSLEEL/HLA-A*24:02Alpha-fetoprotein (357-365) peptide-MHC complexAFP-derived peptide EYILSLEEL presented by HLA-A*24:02

Recognition of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies, leading to the directed lysis of antigen-expressing tumor cells by cytotoxic T-lymphocytes.