Clinical Study on the Safety and Efficacy of CD19-BCMA CAR-T Cell Therapy for Connective Tissue Diseases

• CAR-T (Biological): Eligible subjects who successfully passed screening will receive CAR-T cell infusion on Day 0 after lymphodepleting preconditioning chemotherapy.

Primary outcomes

• Evaluation of Safety [Up to 2 years after CAR-T infusion]: Count the Incidence of adverse events

Secondary outcomes

• Effectiveness evaluation [Up to 2 years after CAR-T infusion]: The response rate of the responder index of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (scleroderma SSc), Sjogren's Syndrome, polymyositis/dermatomyositis, and mixed connective tissue disease (MCTD), as well as the changes in scores compared with the baseline value
• Pharmacokinetic parameters [Up to 2 years after CAR-T infusion]: The highest concentration of CAR-T cell expansion in peripheral blood after administration.
• Pharmacodynamic parameters [Up to 2 years after CAR-T infusion]: The peak values of CAR-T-related cytokines, which include at least IL-6 and IFN-γ.

Sex: All, ages: 1 Year to 70 Years

Inclusion Criteria:

1. Good compliance: The patient or their guardian understands and voluntarily signs the informed consent form, and it is expected that all documents, procedures, follow-up examinations and treatments stipulated in the study can be completed.
2. Previously diagnosed with one of the following diseases and meeting the corresponding latest international classification/diagnostic criteria :

   1. Systemic lupus erythematosus (SLE);
   2. Rheumatoid arthritis (RA);
   3. Systemic scleroderma (SSc) ;
   4. Sjogren's Syndrome (SS);
   5. Polymyositis/dermatomyositis (PM/DM);
   6. Mixed connective tissue disease (MCTD).
3. Researchers determine that the disease is in an active stage;
4. At least one autoantibody is positive in the serum or plasma during the screening period;
5. Insufficient response, intolerance or recurrence to at least one standard treatment;
6. The pregnancy test of the female subjects was negative, and the subjects agreed to take effective contraceptive measures throughout the trial period.
7. The patient's major tissues and organs are functioning well.

Exclusion Criteria:

1. Intracranial hypertension or confusion;
2. Symptomatic heart failure or severe arrhythmia;
3. Respiratory failure;
4. Accompanied by other types of malignant tumors;
5. Diffuse vascular coagulation;
6. Serum creatinine and/or urea nitrogen ≥ 1.5 times the normal value;
7. Sepsis or other difficult-to-control infections;
8. Uncontrollable diabetes;
9. Severe mental disorder;
10. Cranial magnetic resonance imaging (MRI) examination revealed obvious lesions in the intracranial cavity.
11. WHO physical status classification ≥ level 3;
12. Organ transplant recipients;
13. Pregnant and lactating women;
14. HIV+，HBV，HCV，EBV，CMV.

• Yuelin He, Ph.D. degree, Principal investigator, Dongguan Taixin Hospital
• Lan He, Ph.D. degree, Principal investigator, Dongguan Taixin Hospital