Safety and Efficacy of SWK002 in Patients with D2T-Rheumatoid Arthritis

Inclusion Criteria:

1. no gender restriction and age of 18 years and above at the time of signing theinformed consent form.

2. written informed consent approved by the Ethics Committee must be signed in personby all subjects or guardians prior to the commencement of any screening procedure.

3. adult refractory patients who meet the 2010 ACR / EULAR RA diagnostic criteria, withrefractory defined as (1) failure of treatment with csDMARDs (2) experiencingfailure of treatment with ≥2 bDMARDs/tsDMARDs with different mechanisms of action (3) meeting one of the following criteria: 1) DAS28-ESR >3.2 or CDAI >10 2)inability to hormone Hormone cannot be reduced to less than 7.5mg/day (3) Number ofswollen joints and/or painful joints ≥3.

4. Stable treatment with 1 or 2 cs DMARD ( s ) prior to enrollment as follows: (1) atleast 12 weeks of methotrexate and at least 4 weeks of administration at a dose of 7.5-25 mg/week (2) at least 4 weeks of stable hydroxychloroquine dose of ≤400 mg/d (3) at least 4 weeks of stable oral salicylsulphadiazepine 1-3 g/d (4) at least 4weeks of stable oral leflunomide 10-20 mg/day Methylphenidate 10-20 mg/d.

5. no active or latent tuberculosis.

6. Adequate organ function: (1) blood creatinine ≤1.5 times the upper limit of normal,or glomerular filtration rate (eGFR) ≥60m/min/1.73m2 as estimated by the MDRDformula (2) and ALT ≤ 5 times the upper limit of normal for the corresponding ageand total bilirubin ≤ 2.0 mg/dl (3) and ≤ 1 grade of dyspnea and oxygen saturation > 91% in room air.

7. hemodynamically stable with a left ventricular ejection fraction (LVEF) ≥45% asdetermined by echocardiography or multichannel radionuclide angiography (MUGA).

8. female subjects of childbearing potential and all male subjects must agree to use ahighly effective method of contraception until at least 12 months after SWK002infusion and until two consecutive PCR assays show no more CAR-T cells in the body.

Exclusion Criteria:

1. malignant tumors.

2. subjects with current or history of CNS disorders such as seizures, cerebrovascularischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease withCNS involvement.

3. previous subjects who have undergone allogeneic hematopoietic stem celltransplantation (HSCT).

4. subjects who have received chemotherapy other than pretreatment chemotherapy within 2 weeks prior to infusion.

5. subjects who have received other investigational drug therapy within 30 days priorto signing the informed consent.

6. active hepatitis B (defined as hepatitis B surface antigen positivity or hepatitis Bcore antibody positivity combined with a hepatitis B virus DNA test value >1000copies/ml) or hepatitis C (HCV RNA positivity) subjects.

7. HIV antibody positive or syphilis spirochete antibody positive subjects.

8. subjects with uncontrolled acute life-threatening bacterial, viral or fungalinfections (e.g., positive blood cultures ≤ 72 hours prior to infusion).

9. subjects who have lost or donated more than 400 mL of blood within 2 months prior toscreening or have received a blood transfusion.

10. any history of definite drug or food allergy, especially to drugs related to thetherapeutic agents (e.g., fludarabine, cyclophosphamide) or product components (e.g., DMSO) used in this trial.

11. any systemic cytotoxic or systemic immunosuppressive agent within 6 months prior toscreening or during the study period, or any localized cytotoxic or localizedimmunosuppressive agent within 30 days or 5 half-lives (whichever is longer) priorto screening or during the study period.

12. pregnancy (as determined by blood pregnancy test) or lactation.

13. prevalence of systemic inflammatory diseases other than RA (except secondarySjogren's syndrome), including but not limited to juvenile chronic arthritis,Crohn's disease, ulcerative colitis, psoriatic arthritis, systemic lupuserythematosus, ankylosing spondylitis, reactive arthropathy, systemic vasculitis, orgout.

14. the existence of unstable angina pectoris and/or myocardial infarction in the 6months prior to signing the informed consent.

15. other conditions that, in the opinion of the investigator, should not be enrolled inthis clinical study, such as poor compliance.