Refractory ANCA Associated Vasculitis and Lupus Nephritis Treated With BCMA-targeting CAR-T Cells

Inclusion Criteria:

1. Age ≥ 18 years old, not exceeding 70 years old (including 70 years old);
2. If the kidneys are involved, estimate the glomerular filtration rate (eGFR) to be ≥ 15mL/minute/1.73 m2;
3. The following test values within 3 days before the collection of mononuclear cellsmeet the following standards:
4. Absolute lymphocyte count: ≥ 0.5 × 10 ^ 9/L [The use of granulocytecolony-stimulating factor (G CSF) is allowed, but subjects are not allowed toreceive this supportive treatment within 7 days before the screening periodlaboratory examination];
5. Absolute neutrophil count: ≥ 1.0 × 10 ^ 9/L [The use of granulocytecolony-stimulating factor (G-CSF) is allowed, but subjects are not allowed toreceive this supportive treatment within 7 days before the screening periodlaboratory examination];
6. Platelets: Subject platelet count ≥ 50 × 10 ^ 9/L (subjects are not allowed toreceive blood transfusion support within 7 days before the screening periodlaboratory examination);
7. Hemoglobin: ≥ 8.0 g/dL (allowing the use of recombinant human erythropoietin) [subjects have not received red blood cell (RBC) infusion within 7 days prior tothe screening period laboratory examination];
8. Creatinine clearance rate: (CrCl) or glomerular filtration rate (GFR) (CockcroftGault formula) ≥ 30 mL/min;
9. Total bilirubin (serum): Total bilirubin (serum) ≤ 1.5 × ULN; Blood bilirubin>1.5 × Gilbert subjects from ULN can be enrolled with the consent of the sponsor
10. AST and ALT: ≤ 3.0 × ULN;
11. Plasma prothrombin time (PT), international standardized ratio (INR), partialprothrombin time (APTT): PT ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN, INR ≤ 1.5 × ULN
12. Willing to sign an informed consent form.
13. • for refractory ANCA-associated vasculitis ①According to the 2022ACR/EULAR criteria, diagnosed with AAV (GPA or MPA subtype), whohas not achieved remission (BVAS score of 0) for ≥ 3 months after receivingstandardized treatment. Severe patients who have previously undergone standardizedtreatment to induce remission and are now relapsing after maintenance therapy; ②Thepatient is currently or has a positive ANCA during the course of the disease; ③Severeillness (severe organ involvement or life-threatening) requiring treatment (BVAS score ≥ 3.0); The definition of severe illness is vasculitis with life-threatening or organmanifestations.
14. • for refractory LN

• According to the 2019 American Society of Rheumatology (ACR) criteria, diagnosedwith systemic lupus erythematosus, within 6 months prior to infusion, confirmedby renal tissue biopsy according to the 2003 International Society of Nephrology (ISN)/Society of Nephropathology (RPS) criteria as active, proliferative lupusnephritis (LN), type III or IV [excluding III (C), IV S (C), and IV G (C)], ortype III/IV combined with type V, And have received standard treatment that isineffective or relapses after disease remission. ②Positive anti-nuclearantibodies (ANA) and/or anti-dsDNA antibodies during the screening period. ③TheSLE Disease Activity Index (SLEDAI-2000) score during the screening period is ≥

8. SLEDAI-2000 clinical score ≥ 6 points, but low complement and/or anti ds-DNApositivity can be selected. ④The estimated survival period is at least 3 months.

Exclusion Criteria:

-Subjects who meet any of the following criteria should be excluded from this study:

1. Pregnant or lactating women;
2. If combined with alveolar hemorrhage, invasive pulmonary ventilation is required;
3. Refractory GPA and MPA: Combined with other autoimmune diseases involving multipleorgan systems, such as EGPA, SLE, IgA vasculitis (Henoch Schönlein), rheumatoidarthritis, inflammatory myositis, anti-glomerular basement membrane disease, orcryoglobulinemia vasculitis;
4. Difficult to treat LN: severe extrarenal clinical manifestations such as lupusencephalopathy, pulmonary hemorrhage, lupus myocarditis, lupus enteritis, and lupuscrisis; Other autoimmune diseases other than combined SLE, includingdermatomyositis/polymyositis, mixed connective tissue disease, systemic sclerosis,rheumatoid arthritis, etc;
5. Individuals who are known to have allergic reactions, hypersensitivity reactions,intolerance, or contraindications to any component of PRG-1801 or drugs that may beused in the study (including fludarabine, cyclophosphamide, tocilizumab, albumin), orhave experienced severe allergic reactions in the past;
6. A history of malignant tumors within 5 years (① subjects with cervical carcinoma insitu who have been completely removed and have not experienced recurrence ormetastasis for at least 3 years may participate in this study. ② subjects with basalcell or squamous cell carcinoma who have been completely removed and have notexperienced recurrence for at least 3 years may participate in this study);
7. Obvious evidence of cardiovascular disease as follows: a N-terminal B-type natriureticpeptide (NT proBNP)>8500ng/L; b. The New York Heart Association (NYHA) classifiesheart failure as Grade IV; c. Patients who received hospitalization for unstableangina or myocardial infarction within 6 months prior to the first administration, orpatients who received percutaneous cardiac intervention and received the most recentstent placement within 6 months or coronary artery bypass grafting within 6 months;
8. Received the following medication treatment within the prescribed time before singlecollection: ① Received B cell depletion therapy such as rituximab within 24 weeks; ②Received biological agents (such as TNF) within 4 weeks or 2 half-lives - Treatmentwith inhibitors, interleukin receptor inhibitors, belizumab, and tamoxifen; ③ Receivedtreatment such as immunosuppressants within 2 weeks or 5 half-lives ; ④ If systemicglucocorticoids need to be used for a long time from 2 weeks before single collectionto the study period, the dose of the hormone should not exceed 10mg/day; ⑤ Receivedplasma exchange or immunosorbent therapy within 24 weeks, and received intravenousimmunoglobulin (IVIG) therapy within 4 weeks.
9. Vaccinate with live/attenuated vaccines within 4 weeks prior to single collection orduring the study period;
10. Chronic and active hepatitis B ( the HBV DNA test is higher than 500IU/ml), hepatitisC (HCV), human immunodeficiency virus (HIV) infection, or syphilis infection;
11. There is an active infection that requires intravenous injection of antibiotics orhospitalization treatment;
12. Major surgery or surgical treatment caused by any reason within 4 weeks prior toenrollment;
13. Any serious and/or uncontrollable comorbidities that the researcher believes mayinterfere with the evaluation during the research process;
14. Participated in other intervention clinical trials within 3 months prior to enrollmentor within 5 drug half-lives (whichever is longer);
15. Other conditions determined by the researcher as unsuitable for lymphocyte clearanceor cell infusion, or other unsuitable patients for study.