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December 8, 2025Blood

Simultaneous high-throughput identification of myeloid leukemia driver mutation-derived public neoantigens and cognate functional TCRs for TCR-T therapy

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Authors

HNHo NgaiDWDuncheng WangSLShoudan Liang

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Overview

Technique identifies neoantigens and T cell receptors in myeloid leukemia, suggesting potential targets for TCR-T therapy.

Key Points

  • This research aims to identify immunogenic neoantigens derived from driver mutations in myeloid leukemia and their corresponding T cell receptors (TCRs).
  • Used mass spectrometry to identify neoantigen-containing peptide:HLA complexes.
  • Transfected driver mutation-containing mRNA tandem minigene constructs into monocyte-derived dendritic cells.
  • Co-cultured dendritic cells with autologous naïve CD8 T cells to expand TCRs specific to neoantigens.
  • Constructed a pooled DNA-barcoded pHLA-tetramer library for T cell staining and sorting.
  • Identified 29 neoantigen pHLA complexes that elicit T cell responses in myeloid leukemia.
  • Demonstrated cytotoxicity of TCR-T cells against primary AML cells presenting these neoantigens.
  • Showed that some neoepitopes were post-translationally modified, affecting TCR recognition.

Cite This Study

Ngai et al. (2025) studied this question.

synapsesocial.com/papers/693624dd4fa91c937236d1e7https://doi.org/10.1182/blood-2025-259
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Also Consider

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  3. 3TCR-T cells targeting a public neoantigen produced by the SF3B1 K700E mutation kill SF3B1-mutant AML/MDS2025
  4. 4Integrated system for screening tumor-specific TCRs, epitopes, and HLA subtypes using single-cell sequencing data2025
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