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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

Engineering CAR T cells with CD38BiTE enhances cytotoxicity in multiple myeloma, suggesting a novel approach against antigen escape.

Key Points

  • This research aims to enhance BCMA-targeted CAR T cell therapy by engineering cells to secrete CD38BiTE.
  • Constructed αBCMA-CAR.CD38BiTE T cells to target BCMA and CD38.
  • Characterized αBCMA-CAR expression using flow cytometry.
  • Validated CD38BiTE secretion with western blot and flow cytometry.
  • Evaluated cytotoxicity of CAR T cells in co-culture assays utilizing immunodeficient mouse models.
  • CD38BiTE is secreted by CAR T cells and binds to both MM cells and T cells.
  • αBCMA-CAR.CD38BiTE cells exhibit up to 90% cytotoxicity against BCMA-positive MM cells after 24h.
  • The cytotoxicity of αBCMA-CAR.CD38BiTE T cells remains high across different E:T ratios: 70% at 1:9 ratio.
  • Secreted CD38BiTE enhances T cell-mediated cytotoxicity against BCMA-negative cells.
  • Higher cell numbers of αBCMA-CAR.CD38BiTE induce fratricide, mitigated by low plating numbers.

Cite This Study

Merve Özdemir (2025) studied this question.

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