Clinical Trial of CD19-targeted CAR-T Therapy for Refractory Juvenile Dermatomyositis

Inclusion Criteria:

1. Age: ≥5 years and <17 years old

2. To meet the diagnostic criteria of JDM, four or five of the following criteria mustbe met:① symmetrical proximal muscle weakness; ②Characteristic skin changes,including positive dermatitis (purplish red rash on upper eyelid with periorbitaledema) and Gottron papules (red patchy squamous papules on the back of knuckles); ③The level of one muscle enzyme in serum was increased; ④ Positive myositis antibody; ⑤Electromyography shows denervation and myopathy; ⑥ Muscle biopsies showed necrosisand inflammation.

3. The classification criteria of RJDM must meet ① and any of the criteria②-④: ①Patients who are intolerant or unresponsive to glucocorticoids and at least 2immunosuppressants, adequate hormone therapy and duration of at least 6 months; ②The disease progresses rapidly and/or involves organs such as lungs, heart andgastrointestinal tract; ③ Calcification of subcutaneous or muscle and joint tissues; ④ Repeated rashes or skin ulcers.

4. myositis specific antibody positive, defined as MDA-5, NXP2, TIF-1γ, Ro-52 and anyother positive;

5. If the patient has SRP or HMGCR antibody positive immune-mediated necrotizingmyopathy equivalent to RJDM, the inclusion criteria of (2) - (4) can be met.

6. The functions of important organs are basically normal:

① Cardiac function: left ventricular ejection fraction (LVEF) ≥55%, no obviousabnormality in electrocardiogram;

② Renal function: eGFR≥30ML/min/1.73m2;

③ Liver function: AST and ALT≤3.0 ULN, total bilirubin ≤2.0×ULN;

④ Lung function: Lung function is basically normal, SpO2≥92%;

7. Have the criteria for simple or intravenous blood collection, and no othercontraindications for cell collection;

8. The subject of childbearing age has a negative urine pregnancy test result andagrees to take effective contraceptive measures during the test period until 1 yearafter the infusion;

9. The patient or his/her guardian agrees to participate in this clinical trial andsigns an informed consent indicating that he/she understands the purpose andprocedure of this clinical trial and is willing to participate in the study.

Exclusion Criteria:

1. Had previously received CAR T cell therapy;

2. Have other autoimmune or rheumatic diseases other than JDM;

3. primary immunodeficiency or severe secondary immunodeficiency that has not beencorrected;

4. accompanied by serious infectious diseases, including but not limited to activetuberculosis, latent tuberculosis infection, active viral hepatitis, etc.;

5. Evidence of active malignant disease or diagnosis of malignant tumor (includinghematological malignancies and solid tumors, except resected and cured skin basalcell carcinoma)

6. Congenital heart disease or history of acute myocardial infarction within 6 monthsbefore screening, or severe arrhythmias (including multi-source frequentsupraventricular tachycardia, ventricular tachycardia, etc.); Or combined with alarge number of pericardial effusion, serious myocarditis, etc.; Or patients withunstable vital signs who need hypertensive drugs to maintain their blood pressure;

7. suffering from other diseases that require long-term use of glucocorticoids orimmunosuppressants;

8. There is an active or uncontrollable infection that requires systemic treatmentwithin 1 week prior to screening;

9. Received solid organ transplantation or hematopoietic stem cell transplantationwithin 3 months before screening; Acute graft-versus-host disease (GVHD) of grade 2or above was present within 2 weeks prior to screening;

10. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positiveand peripheral blood hepatitis B virus (HBV) DNA titer greater than the normalreference value range; Or hepatitis C virus (HCV) antibody positive and peripheralblood hepatitis C virus (HCV) RNA titer greater than the normal reference valuerange; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilistest positive; Or cytomegalovirus (CMV) DNA test positive;

11. Had received live vaccine within 4 weeks prior to screening;

12. Positive blood pregnancy test;

13. Patients with known malignant diseases such as tumors before screening;

14. Patients who had participated in other clinical trials within 3 months prior toenrollment;

15. Situations in which other investigators consider it inappropriate to participate inthe study.