SF3B1 K700E-derived peptide QEVRTISAL presented by HLA-B*44:02 (SF3B1 K700E/HLA-B*44:02)

The SF3B1 K700E-derived peptide QEVRTISAL presented by HLA-B*44:02 is a tumor-specific neoantigen complex that serves as a target for precision cancer immunotherapy. SF3B1 (Splicing factor 3B subunit 1) is a critical component of the U2 small nuclear ribonucleoprotein (snRNP) complex involved in pre-mRNA splicing, and the K700E mutation is a common driver mutation in hematologic malignancies like myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL) (Malcovati et al., 2011). This mutation creates a novel peptide sequence, QEVRTISAL, which is specifically presented by the HLA-B*44:02 MHC class I allele (Lulla et al., 2018). Because this complex is uniquely expressed on the surface of mutated cancer cells and absent on healthy cells, it is an ideal target for T-cell receptor (TCR) engineered T-cell therapies and neoantigen vaccines. Therapeutic strategies targeting this pMHC complex aim to harness the immune system to selectively eliminate tumor cells while minimizing off-target toxicity. Clinical development focuses on identifying high-affinity TCRs that can recognize this specific neoepitope to treat patients who are both SF3B1 K700E positive and HLA-B*44:02 positive.

Other names

SF3B1 K700E neoepitopeQEVRTISAL-HLA-B*44:02 complexHLA-B*44:02-restricted SF3B1 K700E neoantigenSF3B1 K700E pMHC

T-cell receptor (TCR) binding to the peptide-MHC complex, triggering cytotoxic T-lymphocyte (CTL) mediated lysis of the target cell.