In 2021, researchers from the University of Erlangen-Nuremberg in Germany first used CAR-T cell therapy to successfully treat a patient with relapsed/refractory systemic lupus erythematosus (SLE). Since then, numerous clinical trials have been initiated globally to assess the safety and efficacy of CAR-T therapy in B-cell-mediated autoimmune diseases.
Allogeneic CAR-T cells offer unique advantages due to their uniformity, rapid availability, and potential cost-effectiveness, making them a promising option for autoimmune diseases. However, challenges such as graft-versus-host disease (GvHD), allogeneic rejection, potential gene toxicity from gene editing, and infection risk from excessive immunosuppression limit their broader clinical application.
On May 8, 2025, researchers Tong Hongyan and Lin Jin from The First Affiliated Hospital of Zhejiang University School of Medicine, and Du Bing and Liu Mingyao from East China Normal University/Bangyao Biotech, published a study in Cell Research titled: “Allogeneic anti-CD19 CAR-T cells induce remission in refractory systemic lupus erythematosus” [1].
This study demonstrates that a reduced-intensity lymphodepletion regimen using allogeneic CD19-targeted CAR-T cell therapy (TyU19) is both effective and safe for treating relapsed/refractory SLE.
In this investigator-initiated, single-center pilot study (NCT05988216), the team evaluated the safety and efficacy of TyU19 in treating refractory SLE.
TyU19 is a next-generation off-the-shelf CAR-T cell therapy developed by Bangyao Biotech. Using CRISPR-Cas9 gene editing, the therapy modifies CD19-targeted CAR-T cells from healthy donors to overcome immune rejection.
Between September 2023 and September 2024, four young female patients aged 22–24 with refractory SLE (patients S01–S04) were enrolled. Their baseline SELENA-SLEDAI scores ranged from 14 to 26. All had a history of multiple organ involvement, and S01–S03 had prior lupus encephalopathy (inactive at enrollment). They had previously received various immunosuppressants and biologics.
As shown in the treatment protocol, patients S01–S03 underwent lymphodepletion with fludarabine (Days -5, -4, -3) and cyclophosphamide (Days -5, -4). All received 1×106 CAR-T cells/kg on Day 0. Patient S04 had received telitacicept before enrollment and required a 6-week washout. Due to disease flare during washout (joint pain, chest tightness, low fever), she received cyclophosphamide to control symptoms, followed by CAR-T infusion without additional lymphodepletion.
All four patients showed sustained clinical improvement. Within three months, all achieved sustained remission, with SELENA-SLEDAI scores of 0 and PGA scores under 1 at 3–6 months. Symptoms like arthritis (S02, S03, S04), hair loss (S01–S04), and digital vasculitis/ulcers (S01, S04) resolved. Complement factors C3 and C4 normalized within one month, anti-dsDNA antibody levels declined, and proteinuria disappeared. Antibodies to Smith antigen, U1-RNP, and Ro52 also dropped significantly.
Importantly, patient S01 discontinued all immunomodulators and immunosuppressants, including glucocorticoids, by Month 3—achieving drug-free remission. The other three patients continued on low-dose corticosteroids. Gradual tapering may help maintain and consolidate remission.
The most common Grade 3 or 4 adverse events in early weeks were neutropenia, lymphopenia, liver dysfunction, fever, and fatigue, mainly due to lymphodepletion. All patients only experienced Grade 1 cytokine release syndrome (CRS), presenting as fever for 2–3 days. No patients developed immune effector cell-associated neurotoxicity syndrome (ICANS) or GvHD. Cytokines and CRP levels were closely monitored and remained stable. IgA, IgG, and IgM levels decreased post-infusion in S02, S03, and S04. A comparison of hepatitis B antibody titers pre- and post-treatment showed no diminished vaccine response. No infections occurred during hospitalization or follow-up. Patients took acyclovir and sulfamethoxazole until B cell recovery.
Allogeneic CAR-T therapy typically requires more intensive lymphodepletion than autologous approaches, often using anti-CD52 antibodies—raising risks of immunosuppression and severe infections. TyU19, however, uses CRISPR-Cas9 to knock out TRAC, HLA-A, HLA-B, CIITA, and PD-1 genes, offering significant innovation. Unlike conventional CAR-T, TyU19 requires only minimal lymphodepletion, and this study even explored a “no lymphodepletion” protocol. Remarkably, TyU19 still demonstrated strong therapeutic efficacy, opening new avenues for autoimmune disease treatment and showcasing its translational potential.
On July 16, 2024, Bangyao Biotech, in collaboration with East China Normal University and Shanghai Changzheng Hospital, published a study in Cell [2], reporting the successful use of TyU19 to treat one case of refractory immune-mediated necrotizing myopathy and two cases of diffuse cutaneous systemic sclerosis. All three showed deep symptom relief, significant clinical response score improvement, and reversal of inflammation and fibrosis over a six-month follow-up—without CRS or other severe events—proving TyU19’s safety and efficacy in autoimmune diseases.
This marks the first global report of off-the-shelf allogeneic CAR-T therapy successfully treating autoimmune diseases and the first such study published in the top-tier journal Cell.
The Cell Research article represents the first clinical report of using off-the-shelf allogeneic CAR-T cells in refractory SLE, demonstrating remarkable remission and safety, and expanding the therapeutic potential of such therapies for autoimmune diseases.
SLE is characterized by autoantibodies produced by abnormal plasma and B cells. Long-lived plasma cells (LLPCs), typically CD19- CD38hi CD138hi, are major sources of these antibodies and do not express CD19. Before treatment, CD19- BCMA+ cells were observed in S02–S04, but all patients improved significantly post-treatment, with reductions in peripheral BCMA+ and CD19- BCMA+ cells—suggesting TyU19 may achieve long-term benefit by dual targeting (eliminating abnormal B cells + suppressing plasma cell regeneration).
Conclusion: Allogeneic CD19-targeted CAR-T cells (TyU19) show safety and efficacy in treating refractory SLE, with one patient achieving drug-free sustained remission. This highlights allogeneic CAR-T therapy’s potential as a promising option for difficult-to-treat SLE, warranting further investigation into long-term outcomes and treatment optimization.
[2]. Wang, Xiaobing et al. Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis. Cell, Volume 187, Issue 18, 4890 - 4904.e9
