Product-Intrinsic NF-κB-Driven Transcriptional Programs Connote Durability of CAR-T Response in Multiple Myeloma - PubMed
5 hours ago
- #Multiple Myeloma
- #CAR-T Therapy
- #NF-κB Signaling
- Ide-cel CAR-T therapy yields deep responses in relapsed/refractory multiple myeloma, but over half of patients relapse within a year.
- Single-cell RNA sequencing of 40 ide-cel products revealed that durable responses correlate with NF-κB signaling, pro-survival circuits, tonic/chemokine signaling, and higher CAR transgene expression in CD4 CAR-T cells.
- These transcriptional features are linked to improved progression-free and overall survival, independent of baseline clinical factors.
- NF-κB activity is an intrinsic marker of T-cell fitness, characterized by a central memory phenotype and absence of checkpoint receptors, present in marrow and blood T cells before CAR-T manufacturing.
- Pharmacologic NF-κB inhibition reduces CAR-T cytotoxicity and cytokine production in vitro, confirming its functional role in CAR-T efficacy.