TOPLINE:

Allogeneic CD19 chimeric antigen receptor-natural killer (CAR-NK) cell therapy showed promise in patients with relapsed or refractory systemic lupus erythematosus (SLE), with sustained efficacy. The therapy demonstrated a favorable safety profile, with only one case of grade 1 cytokine release syndrome reported.

METHODOLOGY:

• Researchers conducted an open-label, single-arm, prospective case series at a single site in China, involving 18 adults with relapsed or refractory SLE (median age, 37.5 years; 94% female).
• Patients had sustained moderate-to-severe SLE activity (SLE Disease Activity Index 2000 ≥ 8) despite receiving at least two standard therapies or experienced recurrent flares and glucocorticoid dependence.
• Between August 2023 and June 2024, participants received three infusions of allogeneic CD19 CAR-NK cells at escalating dose levels, with intervals of 3-7 days, following conditioning chemotherapy with fludarabine and cyclophosphamide.
• The primary endpoints were safety and tolerability, including the incidence of dose-limiting toxicities, immune effector cell-associated neurotoxicity syndrome, or cytokine release syndrome.
• The secondary endpoints included the proportions of patients who attained SLE Responder Index (SRI)-4, -6, and -8, lupus low disease activity state (LLDAS), and Definition Of Remission In SLE (DORIS) 2021 remission criteria.

TAKEAWAY:

• At 6 months, 94% of patients achieved an SRI-6 response, with 76% reaching LLDAS and 59% attaining DORIS remission. This effect was sustained through 12 months, with similar proportions (67%) of those with follow-up data achieving LLDAS and DORIS remission.
• Long-term safety monitoring revealed no disease flares or treatment-related adverse events, with most patients tapering glucocorticoids to ≤ 7.5 mg/d.
• Profound CD19-positive B-cell depletion was observed in 89% of patients, with reconstitution initiating by months 3-4 in most cases.
• The therapy was well-tolerated, with only one patient experiencing a grade 1 cytokine release syndrome event, and no cases of neurotoxicity or dose-limiting toxicities were reported.

IN PRACTICE:

“As the first-in-human application of allogeneic CAR-NK cell therapy in SLE, this study introduces a novel off-the-shelf cell therapy platform aligned with the promise of next-generation cellular immunotherapy. CAR-NK cell therapy offers potential advantages over CAR T-cell approaches, including a lower risk of graft-versus-host disease and a reduced likelihood of CRS [cytokine release syndrome] due to intrinsically lower cytokine production of NK cells,” an expert wrote in a related comment.

SOURCE:

The study was led by Jie Gao, PhD, National Key Laboratory of Immunity and Inflammation, Changhai Hospital, Naval Medical University, Shanghai, China. It was published online on November 12, 2025, in The Lancet.

LIMITATIONS:

The sample size of the study was small. Unclear dosage methods and unequal group sizes affected dose-response assessment. Only some patients received cyclophosphamide before fludarabine-cyclophosphamide and CAR-NK cell therapy, which may have influenced the observed early benefits.

DISCLOSURES:

The study was supported by the Shanghai Municipal Health Commission, Changhai Hospital Affiliated with Naval Medical University, and the National Natural Science Foundation of China. Two authors reported receiving grants from funding sources. One of these authors, along with two others, reported being employees of Rui Therapeutics.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.