Safety and Efficacy of CD19-BCMA Targeted CAR-T Therapy for Refractory Generalized Myasthenia Gravis

Inclusion Criteria:

• Study participants will be selected for this study only if they meet all of thefollowing criteria:

1. Age ≥18 years old and ≤80 years old;

2. The subject signs the informed consent form, is willing and able to comply withthe protocol, complete the research assessment and return for follow-up;

3. To be diagnosed as a patient with systemic MG, the patient is required to havepositive myasthenia-related antibodies (AChR-Ab, Musk-Ab or LRP4) on the basisof typical myasthenic symptoms;

4. Evaluated by the researcher as refractory MG. Refractory MG is defined as:

5. Treatment failed after receiving at least 2 immunosuppressants

6. Definition of treatment failure: 1) Persistent weakness and impairment ofdaily activities; 2) MG aggravation and/or crisis during treatment; 3)Intolerance to immunotherapy due to side effects or comorbidities;

7. Repeated plasma exchange (PE) or intravenous immune globulin (IVIg)treatment is required to control symptoms;

8. The researchers believe that despite the current routine immunotherapy forpatients, MG still imposes a large functional burden on patients.

9. MGFA classification IIa~IVa at screening and baseline;

10. QMGS score ≥11 points or MG-ADL score ≥5 points at screening and baseline, ofwhich the eye score accounts for no more than 50%;

11. Male study participants must agree to take contraceptive measures during thetreatment period and within 1 year after receiving study treatment, and areprohibited from donating sperm throughout the study period;

12. If you are a woman of childbearing potential (WOCBP), you must agree to takecontraceptive measures during treatment and for at least 1 year after receivingstudy treatment. Participants must have a negative serum pregnancy test resultduring screening; a negative urine pregnancy test result must be confirmedbefore receiving CART for the first time.

Exclusion Criteria:

• Prior to screening and the baseline visit, study participants will not be eligiblefor inclusion in the study if they meet any of the following criteria:

1. The researcher believes that there is any medical or mental condition that mayharm the research participant or affect the research participant's ability toparticipate in this study; or any condition that the researcher believes isrelated to poor compliance;

2. Women who are lactating or pregnant, or women who plan to become pregnant atany time within 12 months after receiving CART treatment, or who have a historyof spontaneous abortion or induced abortion within 4 weeks before screening;

3. Study participants have clinically relevant active infections (such as sepsis,pneumonia or abscess) or serious infections (resulting in hospitalization orrequiring antibiotic treatment) within 4 weeks before screening;

4. thymoma that underwent thymectomy within 6 months before baseline or wasplanned to undergo thymectomy during the study, or required chemotherapy and/orradiotherapy at any time;

5. Investigator participants have received live attenuated vaccine vaccinationwithin 8 weeks before screening; or plan to receive live vaccine vaccinationwithin 8 weeks after treatment;

6. Study participants have received rituximab treatment within 6 months beforescreening;

7. Have received tocilizumab or eculizumab treatment within 3 months beforescreening;

8. Have received intravenous human immunoglobulin, plasma exchange, orimmunotherapy within 4 weeks before screening;

9. Those with known serious underlying diseases, such as liver and kidney damage,blood diseases, previous severe cardiovascular disease, severe hypertension,diabetes, and poor blood pressure and blood sugar control;

10. Unresected thymoma (Note: Subjects with benign thymoma resected more than oneyear before screening are eligible. Benign is defined as no known metastasis onpathological examination and no intracystic or extracystic Extension. Imagingstudies must be performed during the screening period to assess thymic status).

11. Any of the following laboratory abnormalities occur during the screening period (one repeat measurement can be performed during the screening period beforerandomization to confirm the results)

12. Elevated liver enzymes (aspartate aminotransferase (AST) or alanineaminotransferase (ALT) > 3 times the upper limit of normal (ULN)).

13. Total bilirubin>1.5 times ULN

14. Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2

15. Abnormal PT or INR, or prolonged APTT >1.5 times ULN

16. Neutrophil count <1000cell/ul

17. Platelet count <50000/mm3

18. Hemoglobin<8.0g/dl

19. Those with a high-risk history of tuberculosis infection or acquiredtuberculosis infection;

20. Known immunodeficiency diseases, including human immunodeficiency virus (HIV)infection;

21. Positive for hepatitis B surface antigen (HBsAg) during the screening period;

22. Receive blood transfusion treatment 4 weeks before screening or during thescreening period;

23. Symptoms worsen rapidly during the lead-in period and enter crisis orpre-crisis state (MGFA IVb-V)

24. Other circumstances in which the researcher deems it inappropriate toparticipate in the study.