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December 8, 2025BloodOpen Access

Balancing efficacy and safety: IL-15 BCMA CAR-T cells vs. 2nd generation CAR-T in preclinical myeloma model

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Authors

EVErica VidalRFRui M. FerreiraNHNelson Hamerschlak

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Overview

Preclinical model demonstrates improved antitumor activity of IL-15 BCMA CAR-T cells over 2nd generation CAR-T, highlighting cytokine impact on tumor control.

Key Points

  • To compare the efficacy and safety of IL-15 BCMA CAR-T cells against 2nd generation CAR-T cells in myeloma.
  • Generated primary human T cells targeting BCMA through lentivirus transduction with CAR constructs
  • Evaluated transduction efficiency and T-cell expansion
  • Conducted co-culture assays to measure cytotoxicity against myeloma cell lines
  • Performed in vivo studies on NSG mice engrafted with myeloma cells and treated with CAR-T cells
  • IL-15 BCMA CAR-T cells showed superior antitumor activity compared to 2nd generation CAR-T cells
  • 2nd generation CAR-T cells achieved durable disease control with minimal toxicity, median survival 125 days
  • 4th generation CAR-T cells caused significant toxicity and reduced mouse survival within 35 days
  • Cytokine-secreting cells demonstrated robust IFN-γ and TNF-α production without T-cell exhaustion

Cite This Study

Vidal et al. (2025) studied this question.

synapsesocial.com/papers/69362f3d4fa91c937236d533https://doi.org/10.1182/blood-2025-7635
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