Dual-Targeting BCMA-CD19 CAR-T Cell Therapy in Systemic Lupus Erythematosus: Single-Cell and Immune Repertoire Analysis Reveals Mechanisms of Immune Reconstitution - PubMed
5 days ago
- #Systemic Lupus Erythematosus
- #CAR-T therapy
- #Immune Reconstitution
- Investigates peripheral immune reconstitution post BCMA-CD19 dual-targeting CAR-T therapy in SLE patients.
- Uses scRNA-seq and BCR/TCR sequencing on PBMCs from five SLE patients pre and post therapy (median 90 days).
- Compares with public datasets from CD19 single-targeting CAR-T patients and healthy controls (total 15 subjects, 176,182 cells analyzed).
- Dual-targeting CAR-T depletes B-lineage populations more effectively, including plasma-lineage clusters persistent after CD19 therapy.
- Shows greater suppression of RIG-I/MDA5 and type I interferon transcriptional programs in B cells with dual targeting.
- BCR repertoires shift toward IGHM-dominant, naïve-biased profiles, restoring diversity toward healthy-like states.
- Significant clinical improvement observed (mean SLEDAI decreased from 9.6 to 2.4).
- Suggests dual targeting may offer more comprehensive humoral reset in SLE, warranting further comparative studies.