CD19-Directed Chimeric Antigen Receptor Autologous T Cells (CART19) for Lupus

Inclusion Criteria:

1. Signed informed consent form must be obtained prior to any study procedure. Labs orother procedures obtained during routine clinical care may be used for eligibilityif obtained within the protocol required window.

2. Patient age must be 12-29 years, inclusive, at time of enrollment.

3. Meeting ACR/EULAR Classification Criteria for SLE

4. ANA positive > 1:80 and/or double-stranded DNA (dsDNA) positive

5. Active (refractory) disease, defined as follows: a. Lupus nephritis subjects must meet both the following criteria: i. ISN/RPS activenephritis Class III/IV +/- V lupus nephritis diagnosed by biopsy within past 12months.

ii. Persistent and clinically significant: ≥2 measurements with urine protein with either of the following:

1. > 1mg/mg creatinine

2. > 0.5 mg/mg creatinine associated with renal dysfunction or low albumin.

3. > 0.5 mg/mg creatinine in a patient with rising proteinuria after prior completerenal response b. Non-renal SLE subjects must meet either of the following criteria:i. SLEDAI-2K ≥ 8 and clinical SLEDAI-2K ≥ 6 ii. Inability to decrease prednisone ≤7.5mg/day or 0.15mg/kg/day, whichever is lower, due to active disease.

4. Patients must have had at least 3 months of cumulative conventional therapy defined as:

5. Conventional induction immunosuppressive agent(s) (e.g., mycophenolate mofetil,cyclophosphamide), and

6. At least one additional therapy:

i. B-cell directed biologic therapy (e.g., rituximab, belimumab, ofatumumab, obinutuzumab) ii. Calcineurin inhibitor (e.g., tacrolimus, cyclosporine, voclosporin) iii. Other immunosuppressive medication for SLE (e.g., anifrolumab, abatacept, JAK inhibitor) 7. Adequate organ function status

1. Renal: eGFR must be ≥30 and subject cannot be receiving dialysis.

2. Hepatic: Transaminases < 5x upper limit of normal and serum conjugated (Direct)bilirubin <1.5x upper limit of normal unless attributable to SLE. If attributable toautoimmune disease, Child-Pugh score must be class A or class B. Child-Pugh scorecannot be class C.

3. Cardiac: Shortening fraction > 28%, left ventricular ejection fraction >45%, and noevidence of severe pulmonary hypertension

4. Pulmonary: Must have a minimum level of pulmonary reserve defined as ≤ Grade 1dyspnea and <Grade 3 hypoxia; DLCO ≥40% (corrected for anemia and/or VA volume ifnecessary) if PFTs are clinically appropriate as determined by the treatinginvestigator.

5. Subjects of reproductive potential must agree to use acceptable birth controlmethods.

Exclusion Criteria:

1. Active, untreated infections

2. HIV infection

3. Active Hepatitis B a. Patients must have a negative hepatitis B surface antigen to be enrolled on thisstudy.

4. Active Hepatitis C

5. Patients with severe neuropsychiatric lupus or neurologic manifestations of SLE (e.g. stroke, seizure, psychosis, demyelinating syndromes, organic brain syndrome,or lupus related headaches)

6. Monogenic lupus (known)

7. Previous autologous or allogenic stem cell transplant

8. Previous kidney transplant

9. History of seizure disorder

10. Patients who are on anti-epileptic therapy

11. Participation in a clinical trial in which the patient receives an investigationaldrug within a time period equal or less than 5.5 half-lives of the investigationalagent prior to study enrollment.

12. Subjects who are unwilling or unable to discontinue immunosuppressive medications atthe times of CART19 infusion will be excluded from the trial

13. Any comorbidity that in the opinion of the investigators would jeopardize theability of the subject to tolerate therapy.

14. Pregnant patients. All participants of childbearing potential must have negativepregnancy test.

15. Lactating participants who want to continue breastfeeding.

16. Patients who are unwilling to consent to LTFU