Tumor-associated antigens presented by HLA-A1 (TAA/HLA-A1)

Tumor-associated antigens (TAAs) presented by HLA-A1 (HLA-A*01) represent a critical class of targets for cancer immunotherapy, specifically for T-cell receptor (TCR) engineered T-cell therapies. HLA-A1 is a Major Histocompatibility Complex (MHC) Class I molecule that presents short peptide fragments derived from intracellular proteins, such as MAGE-A3 and MAGE-A1, on the cell surface for recognition by CD8+ cytotoxic T lymphocytes. These peptide-HLA complexes are highly attractive targets because many of the source proteins are cancer-testis antigens (CTAs) that are overexpressed in various malignancies but largely absent in normal adult tissues. HLA-A1 is one of the most prevalent MHC Class I alleles in Caucasian populations, making these targets relevant for a significant portion of cancer patients. However, therapeutic development has faced major safety hurdles, most notably fatal cardiotoxicity in early clinical trials caused by TCR cross-reactivity with the muscle protein Titin. Current research, including programs from companies like TScan Therapeutics, focuses on utilizing advanced screening platforms to identify high-affinity TCRs with improved specificity to minimize off-target risks while maximizing anti-tumor efficacy.

Other names

HLA-A*01 restricted tumor antigensHLA-A1/peptide complexesMAGE-A3/HLA-A1 complexMAGE-A1/HLA-A1 complexpMHC-A1HLA-A1 restricted cancer-testis antigens

T-cell receptor (TCR) mediated recognition and killing of tumor cells via adoptive T-cell therapy or active immunization.