A Clinical Study of CD19 Universal CAR-γδT Cells in Active Systemic Lupus Erythematosus

Exclusion Criteria31

• Known hypersensitivity to prednisone, immunosuppressive agents;
• Diagnosis of active severe lupus nephritis within 8 weeks prior to screening, requiring medications prohibited by the research protocol for active nephritis, hemodialysis or prednisone ≥ 100 mg/d, or equivalent glucocorticoid therapy for ≥14 days;
• Suicidal ideation within the past 6 months based on assessment by Columbia-Suicide Severity Rating Scale (C-SSRS) at screening; or any suicidal behaviors within the past 12 months or recurrent suicidal behaviors during the subject's lifetime;
• Presence of SLE or non-SLE related central nervous system diseases or pathological changes within 8 weeks prior to screening;
• Existence of other lupus crisis within 8 weeks prior to screening;
• Previous or current diagnosis of non-SLE-related inflammatory arthropathy or skin diseases;
• Previous or current diagnosis of severe vasculitis due to other diseases excluding SLE;
• History of vital organ transplantation or hematopoietic stem cell/or bone marrow transplantation;
• Have received plasmapheresis, hemodialysis, intravenous immunoglobulin within 14 days prior to screening;
• Other autoimmune diseases requiring systemic therapy;
• Active or latent tuberculosis at screening (can be enrolled if appropriately treated);
• Any of severe laboratory abnormalities in liver function, renal function, bone marrow function, coagulation function, pulmonary function, cardiac function at screening;
• History of severe allergy or known hypersensitivity to any of the active ingredients of the drugs, excipients, or rodent-derived products, xenoproteins included in this trial, or subjects with allergic constitution;
• Severe heart diseases;
• Severe hepatobiliary disease;
• Presence of medical conditions that are obviously unstable or not effectively treated;
• Presence of uncontrollable bacterial, fungal, viral or other infections, requiring antibiotic therapy;
• Have received live/attenuated vaccination within 4 weeks prior to screening or plan to receive live/attenuated vaccination throughout the study;
• Have received any commercially available Janus kinase inhibitor or Bruton tyrosine kinase inhibitor within 3 half-lives prior to screening;
• Have received B-cell targeted therapy prior to screening;
• Have received a biologic agent other than B-cell targeted therapy within 5 half-lives prior to screening;
• Previous received therapies with CAR-T cells or other genetically modified T cells;
• Have received therapeutic dose of corticosteroids within 7 days prior to leukapheresis or within 72 hours prior to infusion;
• Subjects that have undergone major surgery within 4 weeks prior to lymph depletion or those who are scheduled to undergo major surgery during the study period, or whose surgical wounds have not fully healed prior to enrollment;
• Subjects that have donated blood for ≥ 400mL or had significant blood loss equivalent to at least 400mL within 4 weeks prior to screening, or have received a blood transfusion within 8 weeks, or plan to donate blood during the study period;
• History of ≥ grade 2 bleeding within 4 weeks prior to screening or need for long-term continuous anticoagulant therapy;
• Subjects with severe mental illness;
• Alcoholics or subjects with a history of drug abuse;
• Female subjects who are pregnant or lactating, or intend to pursue pregnancy within 2 years after the cell infusion; male patients whose female sexual partners intend to conceive within 2 years after the cell infusion;
• History of malignancy；
• Patients that have contraindications to any of the study procedures or have other medical conditions that may expose them to unacceptable risk, in the judgment of the investigators and/or clinical criteria.