T-cell receptor recognizing HLA-A*02:01-restricted tumor antigen (TCR/HLA-A*02:01)

The T-cell receptor (TCR) recognizing HLA-A*02:01-restricted tumor peptides is a critical component of the adaptive immune system's ability to identify and eliminate malignant cells. These receptors, located on the surface of CD8-positive cytotoxic T lymphocytes, specifically bind to short peptide fragments derived from intracellular tumor antigens that are presented by the Human Leukocyte Antigen (HLA) A*02:01 molecule. HLA-A*02:01 is one of the most common MHC class I alleles in Caucasian populations, making it a primary focus for the development of precision immunotherapies. In therapeutic applications, these TCRs are utilized in two main formats: TCR-engineered T-cell therapy (TCR-T) and bispecific T-cell engagers. In TCR-T therapy, a patient's own T-cells are genetically modified to express a high-affinity TCR specific for a tumor antigen like MAGE-A4 or NY-ESO-1. Alternatively, soluble bispecific molecules (ImmTACs) use a high-affinity TCR domain to tether T-cells to tumor cells, bypassing the need for the T-cell's endogenous receptor. These strategies aim to overcome the limitations of traditional checkpoint inhibitors by targeting specific intracellular proteins that are otherwise invisible to the immune system (PMID: 33440134, PMID: 35068505).

Other names

HLA-A*02:01-restricted T-cell receptorTumor-specific T-cell receptorMHC-restricted T-cell receptorCD8+ T-cell receptorAntigen-specific T-cell receptor

Drugs targeting or utilizing these receptors typically function as TCR-engineered T-cell therapies (TCR-T) or TCR-bispecific fusion proteins (ImmTACs). TCR-T cells are modified to express a high-affinity TCR that recognizes specific tumor peptides presented by HLA-A*02:01, leading to direct T-cell mediated lysis of cancer cells. Bispecific molecules like Tebentafusp bind the HLA-peptide complex with a TCR domain and recruit effector T-cells via a CD3-binding domain to induce an immune response against the target cell (PMID: 34554482, PMID: 30104715).