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December 8, 2025Blood

CD38BiTE-secretion overcomes antigen escape in BCMA-targeted CAR T cell therapy for multiple myeloma

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Authors

MÖMerve Özdemir

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Overview

Engineered CAR T cells demonstrate improved cytotoxicity against multiple myeloma, targeting both BCMA and immunosuppressive cells, suggesting enhanced therapy efficacy.

Key Points

  • To develop BCMA-targeted CAR T cells that secrete CD38BiTE to overcome antigen escape and improve treatment for multiple myeloma.
  • Constructed CD38BiTE-secreting CAR T cells targeting both BCMA and CD38.
  • Characterized CAR expression via flow cytometry and validated CD38BiTE secretion through western blot.
  • Evaluated cytotoxicity using co-culture and transwell assays in vitro.
  • Established immunodeficient mouse models to assess functional advantages of the engineered CAR T cells.
  • CD38-positive immunosuppressive cells reduced CAR T cell efficiency.
  • αBCMA-CAR.CD38BiTE cells showed up to 90% cytotoxicity against BCMA-positive MM cells at an E:T ratio of 9:1.
  • Secretion of CD38BiTE led to significant cytotoxicity against BCMA-negative MM cells and specific killing of CD38-positive Tregs.

Cite This Study

Merve Özdemir (2025) studied this question.

synapsesocial.com/papers/693624d74fa91c937236d165https://doi.org/10.1182/blood-2025-5848
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Also Consider

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

  1. 1Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed/refractory multiple myeloma: a meta-analysis of interventional and real-world studies2025 · 11 citations
  2. 2Data from Bicistronic CAR T Cell against BCMA and CD229 Effectively Controls Myeloma Even When BCMA Expression Is Limited2025
  3. 3Development of novel MZB1-directed HLA-dependent CAR T cell and CAR enhancer therapy in MM and other B-cell malignancies2025
  4. 4Targeting of tumor antigen CD38 and stress antigens MICA/B by CAR T cells provides a unique approach for the comprehensive treatment of multiple myeloma2025
  5. 5Balancing efficacy and safety: IL-15 BCMA CAR-T cells vs. 2nd generation CAR-T in preclinical myeloma model2025