From April to December 2023, a Phase I/II study enrolled six patients with severe refractory systemic lupus erythematosus (srSLE) to investigate the novel CAR-T cell therapy, YTB323 (rapcabtagene autoleucel). The study provided safety, pharmacokinetic/pharmacodynamic (PK/PD), and preliminary efficacy data. By August 2023, three patients had received treatment, offering insights into early responses. As anticipated, all six patients experienced transient lymphodepletion-related cytopenia, with Grade 3 or 4 events observed in each case, including anaemia in three patients and neutropenia in five. Hypogammaglobulinemia, a frequent adverse event, did not necessitate intravenous immunoglobulin treatment. Cytokine release syndrome (CRS) occurred in four patients, all resolving with tocilizumab treatment at Grades 1 or 2, and no instances of immune cell-associated neurotoxicity syndrome were reported. One patient developed Grade 2 pneumonia as an infectious complication.

The PK/PD studies of the first three patients indicated peak expansion of CAR-T cells between 13 to 21 days post-infusion, coinciding with profound B-cell depletion followed by gradual recovery. Preliminary efficacy assessments demonstrated substantial reductions in the SLE Disease Activity Index (SLEDAI) and Physician Global Assessment (PhGA) scores for these patients. Concurrent improvements were noted in disease biomarkers such as autoantibodies, complement levels, and proteinuria. These early findings suggest a favorable initial response to YTB323 therapy in terms of disease control and biomarker modulation, highlighting its potential as a therapeutic option for srSLE.

Conclusion

CAR-T therapy, an innovative immune cell therapy, which has revolutionized the treatment landscape of haematological malignancies, has now emerged as a promising therapeutic avenue for severe autoimmune diseases. CAR-T cells therapies may offer a steroid-free alternative in several autoimmune diseases. In the emerging pipeline CAR-T cell therapy such as Rapcabtagene autoleucel (Novartis), Descartes-08 (Cartesian Therapeutics), CABA-201 (Cabaletta Bio),  MB-CART19.1 (Miltenyi Biomedicine), and others are anticipated to broaden the treatment landscape for SLE patients in the upcoming years. 

Over the past two years, there have been successful applications of CAR- T constructs targeting CD19 in refractory cases of autoimmune rheumatic diseases such as systemic lupus erythematosus, systemic sclerosis, and anti-synthetase syndrome. Compared to existing therapies that deplete B cells, targeting CD19 has shown faster and more profound therapeutic effects, leading to drug-free remission with manageable side effects. These encouraging outcomes highlight the need for validation through long-term, large-scale randomized controlled studies.

Preliminary findings from the Phase I/II study of YTB323 indicate promising safety, expansion of CAR T-cells, depletion of B-cells, and initial efficacy of YTB323 in severe refractory SLE, underscoring the rationale for ongoing evaluation. Additional patient data and continuous follow-up are currently being collected to further enhance the understanding of its potential benefits.