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The SF3B1 K700E-derived peptide QEVRTISAL presented by HLA-B*44:03 is a tumor-specific neoantigen complex that serves as a target for cancer immunotherapy. SF3B1 is a core component of the U2 small nuclear ribonucleoprotein (snRNP) complex involved in pre-mRNA splicing, and the K700E substitution is a frequent driver mutation in various hematologic and solid malignancies, including myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). This mutation results in the presentation of the novel nonameric peptide QEVRTISAL on the cell surface via the HLA-B*44:03 molecule. Because this specific peptide-MHC complex is absent in healthy tissues, it provides a unique opportunity for highly selective therapeutic intervention, such as T-cell receptor (TCR) engineered T-cell therapies or neoantigen-based vaccines. Targeting this neoantigen aims to induce a potent cytotoxic T-lymphocyte response specifically against tumor cells harboring the SF3B1 mutation. Current therapeutic development focuses on ensuring high affinity for the pMHC complex while maintaining strict specificity to avoid cross-reactivity with the wild-type SF3B1 protein or other self-peptides.
T-cell receptor (TCR) mediated recognition of the peptide-MHC complex on the tumor cell surface, leading to the activation of cytotoxic T-lymphocytes and subsequent tumor cell lysis.
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