PRAME-derived peptide–HLA-A*02:01 complex (PRAME/HLA-A*02:01 complex)

The PRAME-derived peptide–HLA-A*02:01 complex is a therapeutically actionable immune target, comprised of a peptide processed from the cancer-testis antigen PRAME and presented by MHC class I molecule HLA-A*02:01 at the surface of cancer cells. This complex is directly recognized by cytotoxic T lymphocytes or by engineered therapeutic receptors such as specific TCR transgenic T cells and TCR mimic antibodies. Expression of PRAME and subsequent display of this peptide–HLA complex is prevalent in several tumor types (e.g., melanoma, ovarian cancer, sarcoma, AML) but is generally absent or minimal in normal tissues, supporting its utility for immunotherapeutic targeting. Multiple clinical trials are underway using engineered TCR therapies (e.g., IMA203) to target this complex, with ongoing evaluation of specificity, on-target/off-tumor toxicity, and efficacy in patients with HLA-A*02:01.

Other names

PRAME/HLA-A2 complexPRAME peptide–HLA-A2PRAME p/HLA-A*02:01HLA-A2–restricted PRAME peptide complex

T cell receptor engagement: recognition of the PRAME peptide–HLA-A*02:01 complex triggers cytotoxic activity by T cells or engineered TCR therapies. Antibody engagement (TCR-mimic antibodies): binding of TCR-mimic antibodies induces targeted cell death or immune clearance of PRAME-expressing tumor cells.