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.
Age between 18-80 years (inclusive), male or female.
Positive expression of CD19 on peripheral blood B cells by flow cytometry.
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.
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.
History of severe drug allergies or allergic constitution.
Presence or suspicion of uncontrolled or treatment-requiring fungal, bacterial, viral, or other infections.
Central nervous system (CNS) diseases caused by autoimmune or non-autoimmune conditions, including epilepsy, psychiatric disorders, organic brain syndrome, cerebrovascular accidents, encephalitis, or CNS vasculitis.
Dysfunction of major organs not meeting the following criteria (exceptions allowed if abnormalities are caused by autoimmune disease): a. Bone marrow function: White blood cell count ≥3×10⁹/L. Neutrophil count ≥1×10⁹/L (without GSF treatment within 2 weeks prior to testing). Hemoglobin ≥60 g/L. Platelet count ≥50×10⁹/L. b. Liver function: ALT ≤3×ULN (exceptions for ALT elevation caused by inflammatory myopathy). AST ≤3×ULN (exceptions for AST elevation caused by inflammatory myopathy). IBIL ≤1.5×ULN (exceptions for Gilbert's syndrome). Total bilirubin ≤3.0×ULN. c. Renal function: Creatinine clearance (CrCl) ≥30 mL/min (calculated using the Cockcroft/Gault formula, exceptions for acute CrCl decline caused by the disease itself). d. Coagulation function: International normalized ratio (INR) ≤1.5×ULN. Prothrombin time (PT) ≤1.5×ULN. e. Cardiac function: Stable hemodynamics.
Single group
anti-CD19 CAR T cell therapy
Biological/Vaccineanti-CD19 CAR-γδ T cell therapy
Safety of QH103（anti-CD19 CAR-γδT cells）
Incidence of Treatment-Emergent Adverse Events (AEs) in this study. AEs are defined as any adverse medical events occurring from the initiation of lymphodepleting chemotherapy to 12 months after the completion of QH103 cell infusion. The incidence, duration, severity, and management of all adverse events occurring after the participants' enrollment will be recorded and evaluated.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Graft-versus-host disease (GVHD) will be graded based on the criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v5.0).
Maximum tolerated dose of CD19 CAR-γδT cells
Dose-limiting toxicity after cell infusion
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2000) score
The change from baseline in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2000) score at Month 3, 6, 9, and 12.
SRI-4 response
SLE patients who met all three of the following conditions at month3,6,9, and 12 after infusion, achieve SRI-4 response: 1. The SLEDAI-2K rating dropped by at least 4 points 2. No deterioration in PGA scores on a 3-point scale (deterioration is defined as an increase of ≥0.3 points from baseline score) 3. No new manifestations of organ system involvement (new system involvement is defined as one or more new symptoms of BILAG grade A or two or more symptoms of BILAG B)
Sjögren's Tool for Assessing Response (STAR) score
The changes from baseline in the Sjögren's Tool for Assessing Response (STAR) score at Month 3, 6, 9, and 12.
EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)
The changes from baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) at Month 3, 6, 9, and 12.
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