• Patients at least 18 years of age.

• Signed and dated informed consent before the conduct of any trial-specific procedure.

• SLE fulfilling the 2019 ACR/EULAR classification criteria (refer to Appendix 8).

• One BILAG A or two BILAG B despite treatment with at least two of the following treatment options: MMF, cyclophosphamide, rituximab belimumab, anifrolumab, methotrexate, azathioprine.

• SLE with major organ involvement defined as either:

‣ Presence of active lupus nephritis according to the following criteria:

• Histology proven class III or IV lupus nephritis according to ISN/RPS 2003 classification

∙ Urine protein-to-creatinine ratio (UPCR) \>1 in 24-hour urine collection

∙ Glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m2

∙ No history of kidney transplantation.

⁃ Lupus with heart involvement (e.g., myocarditis, pericarditis, endocarditis) as measured by MRI or echocardiography/ultrasound.

⁃ Lupus with pulmonary involvement (Lupus pleuritis, pulmonary arterial hypertension (PAH)) or lung disease defined as:

• Forced Vital Capacity (FVC) ≥ 60 % OR

∙ Forced Expiratory Volume (FEV1) ≥ 60 %,Total Lung Capacity (TLC) ≥ 60 %, DLCO (diffusion capacity) ≥ 60 % (according to ATS/ERS guidelines).

• Absolute CD3+ T cell count ≥ 100/µl.

• No childbearing potential or negative pregnancy test at screening and before chemotherapy in women with childbearing potential. Subjects must agree to use a contraceptive method from screening until 12 months after the administration of the IMP.

• Fully vaccinated against SARS-CoV-2 according to the recommendations of RKI or confirmed SARS-CoV-2 infection within the last 6 months.