ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
A BPTF-specific PROTAC degrader enhances NK cell-based cancer immunotherapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- BPTF is essential for vaccine-induced germinal center B cell responses.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- The dual roles of natural killer cells in liver immunity and tolerance: Implications for health and disease.Hepatology communications · 2026Review
- Unraveling the FGFR-RNA splicing axis: Mechanisms, oncogenic crosstalks and innovations for therapeutic purpose.Acta pharmaceutica Sinica. B · 2026Review
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- Micropeptides in the oncological dark matter: decoding their roles in tumor progression and therapy resistance.Journal of translational medicine · 2025Review
- Recognition of molecular clusters and a novel prognostic signature based on natural killer cell-related genes in skin cutaneous melanoma.World journal of surgical oncology · 2025Article
- Targeting PARylated RACK1/HIF-1Acta pharmaceutica Sinica. B · 2025Article
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Authors and funding
16 authors.
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Abstract
Natural killer (NK) cell-based immunotherapy shows promise in cancer treatment, but its efficacy remains limited, necessitating the development of novel strategies. In this study, we demonstrate that the epigenetic factor bromodomain PHD-finger containing transcription factor (BPTF) hinders hepatocellular carcinoma (HCC) recognition by NK cells through its PHD finger's interpretation of H3K4me3. We have generated a small-molecule proteolysis-targeting chimera (PROTAC) that selectively degrades human and murine BPTF. The degradation of BPTF using PROTACs directly enhances the abundance of natural cytotoxicity receptor ligands on HCC cells, facilitating their recognition by NK cells and thereby augmenting NK cell cytotoxicity against HCC both in vitro and in vivo. Through multidisciplinary techniques, our findings establish targeting BPTF with PROTACs as a promising approach to overcome immune evasion of HCC from NK cells and provide a new strategy to enhance NK cell-based cancer immunotherapy.
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