Piwi-like protein 1-derived peptide presented by HLA-A*02:01 (PIWIL1/HLA-A*02:01 complex)

Piwi-like protein 1 (PIWIL1), also known as HIWI, is a member of the Argonaute family and is classified as a cancer-testis antigen (CTA). While its expression is normally restricted to the germline (testis), it is aberrantly overexpressed in various malignancies, including colorectal, gastric, and lung cancers, where it promotes tumor cell proliferation and invasion. A specific 9-mer peptide derived from PIWIL1, SLSNRLYYL (residues 853-861), is processed and presented on the cell surface by the HLA-A*02:01 major histocompatibility complex. This peptide-MHC complex serves as a highly specific target for immunotherapies, such as Immunocore's IMC-R117C, a bispecific ImmTAC molecule. These therapies use affinity-enhanced T-cell receptors to recognize the complex and an anti-CD3 domain to redirect polyclonal T cells to kill the cancer cells, offering a potential treatment for 'cold' tumors that are resistant to standard checkpoint inhibitors.

Other names

PIWIL1-HLA-A2 complexPIWIL1 peptide-MHCHIWI-derived peptide/HLA-A*02:01SLSNRLYYL-HLA-A*02:01 complex

T-cell redirection via bispecific T-cell receptor (TCR) molecules that bind the peptide-MHC complex and recruit cytotoxic T cells through an anti-CD3 effector domain.