Lupus & antiphospholipid syndrome
Genetically modified CD19-targeting IL-15 secreting natural killer (NK) cells for the treatment of systemic lupus erythematosus
Authors' conclusion
XB-19.15 enables potent, durable B-cell depletion and immune resetting in SLE with off-the-shelf utility and favourable safety.
Study context
- Population
- CD19+ cells (Raji, Nalm6, systemic lupus erythematosus (SLE) B cells), mouse models (Nalm6-luc xenografts, humanised CD34+ mice, SLE PBMC xenografts) and patients with refractory SLErefractory SLE, phase 1
- Participants
- 3 participants
- Comparison
- NK cells engineered with CAR.CD19/IL-15 vs CAR.CD19 alone
Methodological detailspreclinical in vitro and in vivo models, phase 1 proof-of-concept trial
- Preclinical in vitro and in vivo models
- Phase 1 proof-of-concept trial
Main finding
As reported in the abstract
- XB-19.15: superior cytotoxicity, sustained IL-15 secretion and enhanced proliferation in vitro
- Mouse model: significant dose-dependent tumour regression of Nalm-6 and B-cell depletion of humanised mice, with long-term persistence in various lymphoid organs
- SLE xenograft model: total hIgG and anti-dsDNA decreased, with deep clearance of B cells and plasma cells of bone marrow and spleen
- 3 patients receiving XB-19.15: improvement in disease activity and reset of B-cell repertoires
Safety
- Three patients received XB-19.15 without severe adverse events
- Phase 1 proof-of-concept
Original publication
Genetically modified CD19-targeting IL-15 secreting NK cells for the treatment of systemic lupus erythematosus. Ann Rheum Dis. Published 26 August 2025. doi:10.
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