Study to Evaluate the Safety and Preliminary Efficacy of CD19 CAR-T Cell Therapy (TranspoCART19) in Patients With Refractory Lupus Nephritis (CART-NEL)

Inclusion Criteria:

1. Ability and willingness to provide written informed consent.
2. Adults aged ≥18 and ≤65 years with a diagnosis of systemic lupus erythematosus (SLE) according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.
3. Positive antinuclear antibody (ANA) result at a titer >1:80, or positive anti-double stranded DNA (anti-dsDNA), or positive anti-Smith (anti-Sm) antibodies at screening.
4. Diagnosis of class III or IV proliferative lupus nephritis, with or without concomitant class V disease, confirmed by renal biopsy demonstrating active lupus nephritis according to the 2018 ISN/RPS classification.
5. Evidence of refractory or treatment-resistant lupus nephritis according to GLOSEN criteria.
6. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² during the screening period.
7. Urine protein-to-creatinine ratio (UPCR) >0.7 g/g, urine albumin-to-creatinine ratio (UACR) >0.5 g/g, proteinuria >0.7 g/24 h, or albuminuria >0.5 g/24 h at screening with evidence of active lupus nephritis.
8. Stable treatment with an ACE inhibitor, angiotensin receptor blocker and/or mineralocorticoid receptor antagonist (with or without an SGLT2 inhibitor) for at least 3 months prior to screening, unless contraindicated or not tolerated.
9. Adequate venous access and no contraindication to leukapheresis.
10. Women of childbearing potential must have a negative pregnancy test at screening, prior to lymphodepletion and prior to infusion, and must agree to use highly effective contraception. Sexually active men must agree to use condoms and comply with protocol-specified reproductive precautions.
11. Completion of recommended vaccinations, including SARS-CoV-2 vaccination/immunization, before study treatment.
12. Ability and willingness to comply with all study procedures and follow-up requirements.

Exclusion Criteria:

1. Planned initiation of renal replacement therapy during the study period or eGFR <30 mL/min/1.73 m².

2. Severe organ dysfunction, including:

   • Left ventricular ejection fraction (LVEF) <40%.
   • Severe cardiac disease, including recent ischemic heart disease, NYHA class III-IV heart failure, uncontrolled arrhythmias, or severe lupus-related cardiac involvement.
   • Significant hepatic impairment (ALT or AST >1.5× ULN, total bilirubin >1.5× ULN except specified exceptions, INR >1.5).
   • Inadequate hematopoietic reserve (absolute neutrophil count ≤1000/µL, platelets <75,000/µL, leukocytes <3000/µL, lymphocytes ≤300/µL, hemoglobin <8 g/dL).
   • Oxygen saturation <92% on room air.
   • Severe pulmonary disease with compromised respiratory reserve.

3. Active infection requiring treatment during screening or before lymphodepletion.

4. Positive screening for HIV, hepatitis C virus, hepatitis B virus, or evidence of active tuberculosis.

5. Grade ≥2 thromboembolic event within 4 weeks before screening.

6. History of progressive multifocal leukoencephalopathy (PML) or symptoms suggestive of PML.

7. Requirement for systemic glucocorticoids at doses ≥30 mg/day prednisone equivalent.

8. Previous treatment with anti-CD19 CAR-T therapy.

9. Known hypersensitivity or contraindication to TranspoCART19, fludarabine, cyclophosphamide, bendamustine, or required concomitant medications.

10. Concurrent systemic autoimmune disease requiring immunosuppressive therapy independent of SLE treatment.

11. Current or previous malignancy, except adequately treated non-melanoma skin cancer, carcinoma in situ, or malignancy in complete remission for more than 3 years.

12. Previous solid organ transplantation, hematopoietic stem cell transplantation, or bone marrow transplantation.

13. Planned major surgery within one year after study treatment.

14. Receipt of live vaccines within 30 days before administration of the investigational product.

15. Current drug or alcohol abuse that may interfere with study participation.

16. Any severe or uncontrolled medical or psychiatric condition that, in the investigator's opinion, would increase risk or interfere with study participation.

17. Pregnancy or breastfeeding.

18. Women of childbearing potential unwilling to use highly effective contraception throughout the study period.

19. Sexually active men unwilling to use condoms and follow reproductive precautions required by the protocol.

20. Participation in another interventional clinical trial within 90 days before informed consent or receipt of another investigational product within the protocol-specified washout period.

21. Inability or unwillingness to provide informed consent or comply with study requirements.