fourth-gen car t cells targeting bcma/cd19 for refractory systemic lupus erythematosus (sle)

Conditions: Systemic Lupus Erythematosus; Lupus Nephritis; Autoimmune Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granulomatous Polyangiitis; Microscopic Polyangiitis; Systemic Sclerosis; Idiopathic Inflammatory Myopathies; Sjogren's Syndrome

Summary: this study is a preliminary investigation, with a single-group design, not randomized and transparent, focusing on treatment. its purpose is to identify the highest dose of bh002 injection (cd19-bcma car-t cells) that patients suffering from resistant systemic lupus erythematosus can tolerate.

systemic lupus erythematosus (sle) is a type of autoimmune disorder characterized by the creation of autoantibody-generating immune complexes, affecting various systems and organs. in sle, autoreactive b cells can self-activate and morph into plasma cells that produce a high volume of autoantibodies. these cells can also expose their own antigens to autoimmune t cells, thereby stimulating t cells and leading to the release of inflammatory substances. conventional treatment for sle focuses on achieving prolonged remission. in contrast, cd19-bcma car-t cells offer a potential solution by eradicating the abnormal b cells responsible for antibody production. this allows for the rebuilding of the immune system and the restoration of normal immune function in patients, potentially leading to a life free from medication. this highlights the promising potential of car-t therapy in treating sle.

Eligibility criteria:
inclusion criteria: * 18-90 years old; * total score ≥ 10 on the eular/acr 2019 sle classification criteria. * selena-sledai≥8. * patients with cd19+ b-cell. * hemoglobin≥85 g/l. * wbc≥2.5×10\^9/l. * neut≥1×10\^9/l. * bpc≥50×10\^9/l. * ast/alt below 2 times the upper limit of normal; creatinine clearance ≥30 ml/min; blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%. * adequate venous access for apheresis, and no other contraindications for leukapheresis. * women of childbearing age should have a negative serum or urine pregnancy test at screening and baseline. * subjects agree to take effective contraceptive measures during the trial until at least 1 year after car-t cells infusion. * agree to attend follow-up visits as required. * voluntary participation and informed consent signed by the patient or his/her legal/authorized representative. exclusion criteria: * renal disease: severe lupus nephritis (serum creatinine \> 2.5 mg/dl or 221 μmol/l) within 8 weeks --prior to leukapheresis, or subjects who need hemodialysis. * cns disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident \[cva\], encephalitis or cns vasculitis, psychiatric patients with depression or suicidal thoughts. * patients with serious lesions and a history of present illness of vital organs such as the heart, liver,kidney blood and endocrine system. * patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers; * received immunosuppressive therapy within 1 week prior to leukapheresis. * patients with hiv infection; active infection of hepatitis b virus or hepatitis c virus. * patients with syphilis infection. * the presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening. * received live vaccine treatment within 4 weeks prior to screening. * severe allergies or hypersensitivity. * contraindication to cyclophosphamide in combination with fludarabine. * subjects who have undergone major surgery within 2 weeks prior to signing the informed consent form, or who are scheduled to have surgery (other than local anesthetic surgery) during the trial or within 2 weeks of the infusion. * cannula or drainage tubes other than central venous catheters. * pregnant or lactating women, or subjects who plan to have children within 1 year of treatment; * subjects with prior cd19 or bcma-targeted therapy. * participated in any clinical study within 3 months prior to enrollment. * subjects with malignant tumour, except for non-melanoma skin cancer with pfs\>5yr; cervical cancer in situ; bladder cancer; breast cancer.

Keywords: car-t cell therapy