Wilms' tumor 1 peptide (126-134) presented by HLA-A*02:01 (WT1:126-134/HLA-A*02:01)

The WT1:126-134 peptide presented by HLA-A*02:01 is a prominent peptide-major histocompatibility complex (pMHC) target in oncology. It consists of a 9-amino acid sequence (RMFPNAPYL) derived from the Wilms' tumor 1 (WT1) protein, which is processed and presented on the cell surface by the HLA-A*02:01 molecule (Oka et al., 2004, Scientific Reports). WT1 is a transcription factor overexpressed in a wide range of cancers, including acute myeloid leukemia (AML) and various solid tumors, but has restricted expression in healthy tissues, leading the National Cancer Institute to rank it as a top priority antigen for immunotherapy (Cheever et al., 2009, Clinical Cancer Research). This specific pMHC complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, triggering an immune response against the tumor cell. Current therapeutic approaches targeting this complex include TCR-engineered T-cell therapies like JTCR016, bispecific antibodies such as RG6007, and peptide vaccines like galinpepimut-S (BMS, 2023; Roche, 2022; SELLAS Life Sciences, 2024). The clinical utility of this target is restricted to patients who are HLA-A*02:01 positive, necessitating companion diagnostic testing for patient selection.

Other names

WT1 RMF peptideRMFPNAPYL-HLA-A*02:01 complexWT1-A2Wilms' tumor protein 1 (126-134)

T-cell receptor-mediated recognition and subsequent cytotoxic T-lymphocyte activation against cells presenting the WT1 peptide.