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December 8, 2025Blood

TCR-T cells targeting a public neoantigen produced by the SF3B1 K700E mutation kill SF3B1-mutant AML/MDS

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Authors

NTNoah TuboThe University of Texas MD Anderson Cancer CenterYHYanqing HuangGuangxi UniversityXMXizeng MaoThe University of Texas MD Anderson Cancer Center

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Overview

T cell-based therapy shows enhanced cytotoxicity against SF3B1 K700E mutant leukemic stem cells, suggesting a novel treatment for AML/MDS.

Key Points

  • The research investigates the effectiveness of TCR-T cells targeting the SF3B1 K700E neoantigen in treating AML/MDS.
  • Cultured CD8 T cells from healthy donors with SF3B1 K700E peptide to expand specific T cells.
  • Conducted co-culture cytotoxicity experiments to test TCR-T cell activity against mutant and wild type cell lines.
  • Employed NSG CDX-mouse model to evaluate in vivo efficacy of TCR-T cells against SF3B1 K700E leukemia.
  • TCR-T cells demonstrated specificity in killing SF3B1 K700E mutant cell lines while sparing wild type cells.
  • TCR-T cells showed a strong preference for the mutant peptide with high functional avidity.
  • Mice treated with SF3B1 K700E specific T cells had increased survival compared to controls.

Cite This Study

Tubo et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dd9chttps://doi.org/10.1182/blood-2025-2363
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Simultaneous high-throughput identification of myeloid leukemia driver mutation-derived public neoantigens and cognate functional TCRs for TCR-T therapy2025
  2. 2T cells dressed up with a dual HLA-restricted TCR targeting cathepsin G drive effective AML eradication2026 · 1 citations
  3. 3Acute Myeloid Leukemia eradication targeting cathepsin g with a dual HLA-restricted TCR2025
  4. 4A case of co-mutation of SF3B1 and BCR::ABL1 demonstrating an MDS-phenotype2025 · 1 citations
  5. 5SF3B1 mutations K700E, K666N, and R625H: Gene expression and aberrant splicing consequences2025