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December 8, 2025Blood

Novel indirubin-3-monoxime derivative I3MV-8b enhances anti-CD38 monoclonal antibody efficacy in multiple myeloma through dual proteasome and HDAC6 inhibition

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Authors

XZXiaoyu ZhangXSXiyue SunYWYijie Wang

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Overview

Combination of I3MV-8b and anti-CD38 mAbs improves cytotoxicity in multiple myeloma, suggesting enhanced treatment strategies.

Key Points

  • To investigate the effects of compound I3MV-8b on anti-CD38 monoclonal antibody efficacy in multiple myeloma.
  • Utilized NK-humanized NSG mouse model to assess treatment efficacy.
  • Employed RNA-seq and flow cytometry to evaluate CD38 expression changes.
  • Performed ATAC-seq and ChIP-Seq analyses for chromatin accessibility and transcription activity.
  • Conducted multicolor spectral flow cytometry to analyze NK cell populations and functions.
  • Treatment with compound 8b significantly upregulated CD38 expression on MM cells.
  • Combined treatment with daratumumab and compound 8b improved NK cell cytotoxicity in vitro.
  • Increased histone acetylation levels were observed, particularly H3K27ac.
  • Compound 8b enhanced immune cell function, reducing NK cell exhaustion markers.

Cite This Study

Zhang et al. (2025) studied this question.

synapsesocial.com/papers/69362f484fa91c937236d679https://doi.org/10.1182/blood-2025-5708
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Also Consider

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

  1. 1Preclinical characterization of a novel investigational monoclonal antibody CM313 with potent CD38-positive cell killing activity2024 · 8 citations
  2. 2Modulating CD38 enzymatic activity during antibody-based immunotherapy in multiple myeloma: a basic science perspective2026 · 4 citations
  3. 3Abstract 1237: IGM-2644, a CD38xCD3 bispecific IgM T cell engager, shows enhanced anti-tumor activity compared to daratumumab in preclinical models of multiple myeloma2024 · 1 citations
  4. 4Non-Competitive Binding of Isatuximab and Daratumumab to CD38: Implications for Targeted Therapy in Multiple Myeloma2025 · 1 citations
  5. 5Leveraging novel CD38 targeted antibody-drug-conjugates for the treatment of multiple myeloma2025 · 1 citations