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Genetic Disruption of Blimp-1 Drastically Augments the Anti-Tumour Efficacy of BCMA-Targeting CAR-T Cells

GSE255977 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/11/20 Platform GPL24676
Summary
Chimeric antigen receptor-T (CAR-T) cells directed against B-cell maturation antigen (BCMA) are an effective treatment for multiple myeloma, but short persistence and frequent relapses are challenges for this immunotherapy. This lack of durability has been attributed to the premature terminal differentiation of CAR-T cells which prevents the formation of long-lived memory cells that maintain anti-tumour responses. To improve long-term efficacy, we used CRISPR/Cas9-mediated gene editing to ablate the expression of the transcription factor Blimp-1 (Prdm1). In a murine model of advanced myeloma, Blimp-1 knockout (KO) CAR-T cells effectively slowed or even prevented disease progression, significantly outperforming control (Mock) CAR-T cells in improving survival. To understand this enhanced in vivo effectiveness, Blimp-1 KO CAR-T cells were characterised after being repeatedly challenged with tumour cells in vitro and subject to gene expression analysis.
Published in
Genetic disruption of Blimp-1 drastically augments the antitumor efficacy of BCMA-targeting CAR T cells
Battram AM, Mañé-Pujol J, Moreno DF et al. · Blood advances 2025 · PMID 39642314 · doi:10.1182/bloodadvances.2024013209
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Also filed as BioProject PRJNA1077339 and SRA study SRP490050. Searching any of these in the dataset finder brings you back here.

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