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Generation of iPSC-derived CD4+ Th1 cells enhancing chimeric antigen receptor-T cell cytotoxicity

GSE302158 Homo sapiens Expression profiling by high throughput sequencing 17 samples Submitted 2025/07/13 Platform GPL20795
Summary
CD4+ T cells are anticipated to enhance the overall immune response, including the anti-tumor activity of chimeric antigen receptor (CAR)-T cell therapy. In the past, we established a culture system to generate CD8+ T cells from iPS cells (iPSCs); however, it was challenging to generate CD4+ T cells. Drawing inspiration from the observation that adult T cell leukemia (ATL) cells are consistently CD4+ and possess Treg characteristics, we successfully generated CD4+ Treg cells by reprogramming ATL cells into iPSCs and then differentiating them into T cells. Gene expression analysis of this generation system suggested that RUNX3 serves as a key regulator in T cell differentiation within the ex vivo generation system. By knocking out RUNX3, we demonstrated the generation of antigen-specific CD4+ Th1 cells via the iPSC route, thereby enhancing the activity of CD8+ CAR-T cells against GD2-expressing lymphoma. These technologies hold significant promise for contributing to “off-the-shelf” immunotherapies against malignant tumors, including solid tumors.
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Also filed as BioProject PRJNA1289096 and SRA study SRP599628. Searching any of these in the dataset finder brings you back here.

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