Safety and Efficacy of Universal CD19-targeting CAR-γδT Cells in Refractory Autoimmune Diseases

Autoimmune diseases refer to a common category of diseases caused by the immune system reacting to self-antigens, leading to tissue damage. Autoimmune diseases encompass a wide variety of conditions, such as systemic lupus erythematosus（SLE）, Sjögren's syndrome (SS), systemic sclerosis (SSc), inflammatory myopathies (IM), ANCA-associated vasculitis (AAV), and antiphospholipid syndrome (APS). They affect the quality of life, while in severe cases, they can be life-threatening. Additionally, they impose a heavy economic burden on society. Current treatments for autoimmune diseases include glucocorticoid, immunosuppressants, and biologics. B cell-driven humoral immune abnormalities are a central pathogenic mechanism in many autoimmune diseases. When autoreactive B cells are excessively activated, they produce large amounts of autoantibodies and immune complexes. These antibodies and immune complexes can cause damage to various tissues and organs, leading to the development of multiple autoimmune diseases. Therefore, targeting B cells to treat autoimmune diseases is an attractive therapeutic strategy. Chimeric Antigen Receptor (CAR)-T cells targeting the B cell surface molecule CD19 have achieved significant clinical progress in acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma, with several CD19 CAR-T therapies approved for marketing worldwide. Increasingly, clinical studies are exploring the use of CD19 CAR-T cells for the treatment of autoimmune diseases, and their therapeutic efficacy has been demonstrated. In this study, the investigators used γδ T cells as carrier cells to investigate the safety and efficacy of universal CAR-γδ T cells in the treatment of autoimmune diseases.

Inclusion Criteria: Common Inclusion Criteria: 1. Age between 18-80 years (inclusive), male or female. 2. Positive expression of CD19 on peripheral blood B cells by flow cytometry. 3. Diagnosed with refractory autoimmune disease, defined as: Ineffectiveness of conventional treatment for more than 6 months, or Disease activity recurrence after remission. Definition of conventional treatment: Use of glucocorticoids and any of the following immunosuppressants or biologics: cyclophosphamide, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, rituximab, belimumab, telitacicept, etc. 4. Currently receiving one or more standard therapies at a stable dose, including glucocorticoids, antimalarials, immunosuppressants, or biologics. If the subject is receiving glucocorticoids, the following conditions must be met: During screening and the screening period, the maximum dose of glucocorticoids is 30 mg/day prednisone (or an equivalent dose). The glucocorticoid dose must remain stable for ≥7 days before screening, and during the screening period, the dose adjustment must not exceed \>5 mg/day prednisone (or an equivalent dose). If the subject is receiving antimalarials and/or conventional immunosuppressants: The treatment must have started ≥12 weeks before screening. The medication dose must remain stable for ≥8 weeks before screening and throughout the screening period. Before cell infusion, other immunosuppressants (excluding hydroxychloroquine), including belimumab, telitacicept, CD20 monoclonal antibodies, or other biologic immunosuppressants, must be discontinued for at least 5 half-lives. 5. Female participants of childbearing potential and male participants with female partners of childbearing potential must use medically approved contraceptive methods or practice abstinence during the study treatment period and for at least 6 months after the study. Female participants of childbearing potential must have a negative serum HCG test within 7 days before enrollment and must not be breastfeeding. 6. Willing to participate in the trial and sign the informed consent form. Disease-Specific Inclusion Criteria: 1. Systemic Lupus Erythematosus (SLE): * Meets the 2019 EULAR/ACR classification criteria for SLE. * ANA titer ≥1:80, or positive for anti-dsDNA and/or anti-Sm antibodies. * Disease activity score (SLEDAI-2000) ≥8. 2. Sjögren's Syndrome: * Meets the 2002 AECG criteria or the 2016 ACR/EULAR classification criteria for primary Sjögren's syndrome. * Disease activity score (ESSDAI) ≥5. * Positive for anti-SSA/Ro antibodies. 3. Systemic Sclerosis (SSc): * Meets the 2013 EULAR/ACR classification criteria for systemic sclerosis. * Classified by Leroy and Medsger as limited or diffuse cutaneous subsets. * At screening, mRSS \>10; and/or active interstitial lung disease (ILD), defined as: High-resolution computed tomography (HRCT) showing ground-glass opacities. Pulmonary function tests (FVC or DLCO) \