Phase I/II Study of AD-PluReceptor Plus Tafasitamab-cxix and Lymphodepleting Chemotherapy in Patients With Autoimmune Disorders

Inclusion Criteria: SSc Specific Inclusion Criteria A. Diagnosis of SSc defined as follows: i) Fulfilling 2013 American College of Rheumatology (ACR)and European League Against Rheumatism classification (EULAR) criteria for SSc.46 ii) Antinuclear Antibody (ANA) by immunofluorescence positive at titer ≥ 1:80 at screening or prior to screening. B. SSc disease activity i) Diffuse SSc meeting the following criteria: (1) Disease duration ≤ 7 years (from onset of first non-Raynaud manifestation) AND (2) mRSS ≥ 15 at screening (Appendix 1) OR ii) Participants diagnosed with diffuse or limited cutaneous SSc AND presence of ILD changes on HRCT AND Disease duration ≤ 7 years (from onset of first non- Raynaud manifestation) AND either (1) or (2) 1. Progressive ILD as defined by Raghu et al47 (≥ 2 of the following): (a) worsening respiratory symptoms (b) physiological evidence of disease progression (≥ 1 of the following): (i) Absolute decline in FVC ≥ 5% predicted within 1 year of follow-up (ii) Absolute decline in DLCO (corrected for Hb) ≥ 10% predicted within 1 year of follow-up radiological evidence of disease progression (c) radiological evidence of disease progression (≥ 1 of the following): (i) Increased extent or severity of traction bronchiectasis and bronchiolectasis. (ii) New ground-glass opacity with traction bronchiectasis (iii) New fine reticulation (iv) Increased extent or increased coarseness of reticular abnormality. (v) New or increased honeycombing (vi) Increased lobar volume loss 2. FVC \< 80% predicted or extent of ILD changes on HRCT \> 20%. C. Inadequate response to at least 1 of the following treatments used for at least 3 months: mycophenolate, cyclophosphamide, rituximab, and/or tocilizumab SLE Specific Inclusion Criteria 1. A clinical diagnosis of SLE, based on the 2019 EULAR/ ACR classification criteria for adult SLE. 2. Positive ANA titer ≥1:80 or positive anti-dsDNA antibody at screening or prior to screening. 3. For LN subjects only: Active, biopsy-proven lupus nephritis (kidney biopsy should have been done within 1 year of study enrollment) class III or IV, with or without the presence of Class V, using the 2018 Revised International Society of Nephrology/Renal Pathology Society criteria48. 4. Diagnosed with active SLE. Subjects with either LN or without LN will be eligible if they meet the following criteria: a. For LN subjects: urine protein-to-creatinine ratio (UPCR) ≥0.5 g/g on 2 first morning void urine samples during screening despite prior or current treatment with standard of care therapy for at least 12 weeks, including corticosteroids, MMF/mycophenolic acid (MPA), CY, calcineurin inhibitors, belimumab, and/or rituximab. Patients should have failed at least 2 standard of care immunosuppressive therapies tried for 3 months, b. For non-renal SLE subjects: SLEDAI-2K ≥8 and clinical SLEDAI-2K ≥6 (excluding headache, alopecia, mucosal ulcers, fever, and organic brain syndrome) or ≥ 1 major organ system with a BILAG A score (excluding musculoskeletal, mucocutaneous, and/or constitutional organ system) during screening despite prior or current treatment with standard of care therapy, including corticosteroids, rituximab or other B cell depleting agents, CY, MMF/MPA, azathioprine, methotrexate, 6-mercaptopurine, sirolimus, tacrolimus, thalidomide, leflunomide, mizorbine, anifrolumab, and/or belimumab. Patients should have failed at least 2 standard of care immunosuppressive therapies tried for 3 months, or failed due to intolerance, or unable to obtain medication. 5. If a subject is currently receiving: 1. A renin-angiotensin-aldosterone inhibitor, (including direct renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and mineralocorticoid receptor blockers), the subject must be on a stable dose for at least 8 weeks prior to screening. A sodium-glucose cotransporter-2 (SGLT2) inhibitor, the subject must be on a stable dose for at least 8 weeks prior to screening. 2. Regarding oral corticosteroid, doses \<0.5 mg/kg prednisone equivalent at the time of enrollment are required. Steroid taper to ≤10 mg prednisone equivalent prior to lymphodepleting chemotherapy is recommended. Chronic GVHD specific inclusion criteria 1. The patient has a history of steroid resistant chronic graft versus host disease (SR- chronic GVHD) or is intolerant of or has unacceptable complications with steroids. Definition of SR-chronic GVHD - Chronic GVHD that does not respond adequately to full-dose prednisone. Any of the following conditions would be considered SR-chronic GVHD: * Progressive symptoms / manifestations of chronic GVHD despite receiving prednisone 1 mg/kg/day (or equivalent) for two weeks * Stable symptoms / manifestations of chronic GVHD after four to six weeks of prednisone ≥0.5 mg/kg/day (or equivalent) * Inability to taper prednisone to \<0.5 mg/kg/day (or equivalent) without worsening of symptoms / manifestations of chronic GVHD 2. Disease activity: • Manifestations/symptoms of chronic GVHD rated as moderate to severe on the NIH chronic GVHD global severity score. 3. Manifestations/symptoms of chronic GVHD that have not adequately responded or intolerant to both: * Ruxolitinib * Belumosudil. 4. May be receiving adrenal replacement doses of corticosteroids Inclusion Criteria: For SLE, SSc, and chronic GVHD 1. Able to provide informed consent. 2. Age ≥18 to ≤80 years. 3. Adequate organ function i) Peripheral blood absolute neutrophil count (ANC) ≥ 1 × 109/L, unless the neutropenia is deemed to be caused by the underlying autoimmune disease. ii) Hemoglobin ≥ 8 g/dl, unless the anemia is deemed to be caused by the underlying autoimmune disease. iii) Platelet count ≥ 50 × 109/L without platelet transfusion support, unless the thrombocytopenia is deemed to be caused by the underlying autoimmune disease. No clinically significant active bleeding. iv) Aspartate aminotr