What question did this study set out to answer?

To identify neoantigens derived from driver mutations in myeloid leukemia and their corresponding TCRs for TCR-T therapy.

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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Techniques reveal immunogenic neoantigens and TCRs in myeloid leukemia, suggesting novel immunotherapy options.

To identify neoantigens derived from driver mutations in myeloid leukemia and their corresponding TCRs for TCR-T therapy.
Leveraged T cell sensitivity to identify neoantigen-derived pHLA complexes
Used TMG mRNA transfection in dendritic cells for neoantigen presentation
Screened synthetic peptides for HLA binding
Generated and tested TCR-T cells for functional reactivity against identified neoantigens.
Identified multiple TCRs targeting 29 neoantigens in myeloid malignancies
Demonstrated TCR-T cell cytotoxicity against AML cells expressing target mutations
Revealed TCR reactivity to modified neoepitopes, indicating complexity in T cell recognition.

Ngai et al. (2025) studied this question.

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