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December 8, 2025BloodOpen Access

Epigenetic reprogramming via EZH1/2 inhibition enhances T cell-mediated immunotherapies against multiple myeloma

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Authors

MPMartina PucilloZZZhaohui ZhengMHMatthew Ho

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Overview

Inhibition of EZH1/2 improves T cell cytotoxicity and cell differentiation in multiple myeloma, suggesting a dual therapeutic approach.

Key Points

  • This research investigates how EZH1/2 inhibition can improve T cell-mediated immunotherapies in multiple myeloma.
  • Utilized EZH2 inhibitors and dual EZH1/2 inhibitors on MM cell lines in colony formation assays.
  • Combined EZH1/2 inhibitors with anti-BCMA CAR-T and bispecific antibodies in long-term killing assays.
  • Developed a xenograft model of multiple myeloma to assess the therapeutic impact of EZH1/2 inhibition.
  • EZH1/2 inhibitors significantly reduced clonogenic growth of MM cells in vitro.
  • Enhanced cytotoxicity of CAR-T therapy against MM cell lines when combined with EZH1/2 inhibitors.
  • Valemetostat treatment improved response rates from 40% to 80% in xenograft models, enhancing T cell activation.

Cite This Study

Pucillo et al. (2025) studied this question.

synapsesocial.com/papers/69362f5a4fa91c937236db78https://doi.org/10.1182/blood-2025-2160
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Also Consider

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

  1. 1Immune priming with the EZH2 inhibitor tazemetostat in B-cell lymphomas receiving CAR T-cell therapy.2026
  2. 2Genomic alterations in TET2 and EZH2 serve as critical drivers of clonal malignant evolution in anti-BCMA CAR-T therapy for multiple myeloma.2025
  3. 3Abstract 5189: Generating EZH2-inhibitor resistant CAR-T cells to sustain function for combination therapy2026
  4. 4EZH2 inhibition overcomes immunomodulatory drug resistance in multiple myeloma via a cereblon-dependent pathway2026 · 1 citations
  5. 5Abstract PR01: EZH2 inhibitors improve CAR-T therapy by enhancing lymphoma B cell immunogenicity and CAR-T cell functions2024