SF3B1 K700E neoantigen (SF3B1ⁱ⁰⁰⁰ᴿ neoantigen)

The SF3B1 K700E neoantigen arises from a recurrent hotspot mutation (lysine to glutamic acid at position 700) in the SF3B1 gene, a core component of the U2 small nuclear ribonucleoprotein (snRNP) in the spliceosome. This mutation, found in ~20% of MDS patients (80% of MDS with ringed sideroblasts) and associated with progression to AML, generates a leukemia-specific peptide neoantigen naturally processed and presented by HLA-A*02:01 or HLA-B*40:01 on mutant cancer cells, including leukemic stem cells. It enables highly specific CD8+ T-cell recognition and killing by engineered TCR-T cells, sparing wild-type cells, making it a promising shared target for T-cell immunotherapy in SF3B1-mutated myeloid malignancies. The mutation also induces aberrant RNA splicing, affecting pathways like cell proliferation and immune regulation.

Other names

SF3B1K700E neoantigenSF3B1ⁱ⁰⁰⁰ᴿ mutant peptide

T-cell receptor (TCR)-mediated recognition and killing of mutant cells (HLA-A*02:01 or HLA-B*40:01 restricted)