BAFF CAR-T Cells (LMY-922) for Treatment of Refractory Autoimmune Disease

Inclusion Criteria: Participants must meet all the following inclusion criteria to be eligible for enrollment: 1. Male or female 16-75 years of age, inclusive. 2. For participants with: a. Rheumatoid Arthritis: i. Meets criteria for seropositive, adult-onset RA as defined by the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, or seropositive (rheumatoid factor positive) polyarticular juvenile arthritis as defined by the International League of Associations for Rheumatology (ILAR) classification criteria for at least 3 months prior to screening ii. Disease Activity Score DAS28-ESR\>3.2 at screening. iii. At least one swollen joint with Power Doppler activity of at least grade 1 or B-mode activity of at least grade 2 at screening. iv. Inadequate response to at least one csDMARD and at least two tsDMARD/bDMARDs with two different mechanisms of action. v. Rheumatoid factor or ACPA positivity (cut off 20 mU/ml) at screening. b. Systemic Lupus Erythematosus: i. Meets European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria for Systemic Lupus Erythematosus prior to screening ii. Participant must be positive for at least one of the following at screening: Anti-dsDNA (above the upper limit of normal \[ULN\]); or anti-Sm (above the ULN); or anti-chromatin iii. An inadequate response to at least two immunomodulatory agents (cyclophosphamide, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil) and one biologic agent (e.g., belimumab, anifrolumab) iv. Diagnosed with active SLE based on at least one of the following: 1. Active non-renal SLE with SLEDAI score ≥6 at screening; 2. Biopsy proven lupus nephritis (LN) with a urine protein creatinine ratio of ≥1 mg/mg on a first morning void. A biopsy must be performed in the 6 months prior to the screening showing active LN class III or IV, with or without class V, in accordance with the 2018 International Society of Nephrology/Renal Pathology Society classification. c. Dermatomyositis: i. Meets 2017 EULAR/ACR Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies for definite or probable diagnosis of DM or juvenile DM at least 6 months before screening. ii. Positivity for at least one myositis-specific antibody (aminoacyl tRNA synthetases, Mi2, MDA5, SAE, SRP, ARS, HMGCR, MJ, TIF1gamma) iii. Active DM as defined by at least one of the following: Active skin disease as defined by a CDASI-A score of at least 14, or active muscle disease as defined as Manual Muscle Testing (MMT-8) score \<142/150 and creatine kinase, aldolase, LDH, AST, or ALT ≥2×ULN (if deemed due to muscle inflammation by investigator) and MRI evidence of active myositis within last 3 months. iv. Failure of at least 2 standard-of-care therapies, including csDMARDs + corticosteroids and bDMARD or IVIG v. Inadequate response to intravenous immunoglobulin (IVIG) and at least two immunomodulator agents: cyclophosphamide, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil and one biologic agent (e.g., rituximab, belimumab). d. Systemic Sclerosis: i. Per 2013 ACR/EULAR classification criteria and all of the following: 1. Disease duration of ≤ 3 years (time from the first non-Raynaud phenomenon manifestation); 2. mRSS \> 10 at screening with early disease or rapid progression, or mRSS ≥ 15 with disease duration ≥ 18 month.; 3. Positivity for at least one SSc-specific parameter (Scl70, RNA polymerase, Th/To, RP11/12, U3RNP autoantibodies); 4. Failure of treatment with at least 2 standard-of-care therapies, including ≥2 csDMARDs (including mycophenolate or cyclophosphamide) and ≥1 bDMARD (including rituximab); 5. Diffuse SSc with or without interstitial lung disease (ILD) 3. Stable doses of corticosteroids for at least 4 weeks and other immunosuppressives for 8 weeks. 4. Adequate organ function as defined by each of the following: 1. Creatinine clearance more than or equal to 45 ml/min calculated per the 2021 CKD-EPI Creatinine Equation 2. Participants must have adequate cardiac function as defined as left ventricular ejection fraction ≥ 45% on the most recent echocardiogram and no clinically significant arrhythmias, pericardial effusion, valvular, or ischemic heart disease. 3. Adequate pulmonary function with pulse oximetry ≥92% on room air. 4. Total Bilirubin \< 1.5× the institutional upper limit of normal (except in participants with Gilbert's syndrome). 5. ALT (SGPT) and AST (SGOT) \< 1.5× the institutional upper limit of normal (except for participants with active myositis). 6. Hemoglobin ≥ 8.5 g/dL, and no red blood cell transfusion within 60 days before the laboratory test. 7. Platelets ≥ 100,000/μL, no transfusion support within 7 days before the laboratory test, and no associated bleeding. 8. Absolute neutrophil count ≥1000. 5. Participants (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document. 6. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 1 year after the BAFF CAR-T cell infusion. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. 7. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for at least 1 year after the BAFF CART cell infusion. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 1 year after the BAFF CAR-T cell infusion to avoid potential embryonal or fetal exposure. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. 8. Body weight of at least 55kg for participants treated at Dose Level 3 (450 × 10\^6 BAFF+ CAR cells) and at least 37kg for all other dose levels. 9. Participants must be vaccinated per institutional guidelines at least four weeks prior to lymphodepletion. Exclusion Criteria: The presence of any of the following will exclude a participant from study enrollment: 1. Significant disease-related complications a. For Systemic Lupus Erythematosus participants: i. Features of severe neuropsychiatric lupus, including seizures, psychosis, stroke, lupus cerebritis or lupus meningitis. Prior history of severe neuropsychiatric lupus with active features should be discussed with the medical monitor ii. Active secondary hemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS) iii. History of antiphospholipid syndrome diagnosed by ACR/EULAR criteria (isolated obstetric antiphospholipid syndrome is allowed) b. For Dermatomyositis participants: i. Overlap myositis/connective tissue disease (except for overlap with Sjögren's syndrome) ii. Participants with other types of myositis or myopathies: polymyositis, paraneoplastic myositis, inclusion body myositis, metabolic or drug induced myopathy, dystrophies c. For Systemic Sclerosis participants: i. Anticentromere antibody seropositivity ii. SSc mimics (eg, scleromyxedema, eosinophilic fasciitis) iii. Pulmonary arterial hypertension (PAH) as determined by right heart catheterization or on PAH approved medications for PAH. It is acceptable to use PDFE-5 inhibitors for Raynaud's and digital ulcers 2. Active thrombotic thrombocytopenic purpura (TTP)/microthrombotic vasculopathy (TMA) 3. Current or prior malignancy, unless the malignancy was treated with curative intent and the participant has no known active malignant disease present for ≥ 5 years prior to enrollment. 4. Symptomatic congestive heart failure. 5. Renal failure requiring regular dialysis. 6. Uncontrolled pulmonary disease. 7. Ongoing infection, whether controlled or uncontrolled. 8. Cardiovascular disorders including unstable angina pectoris, clinically significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack, or other ischemic event) within 6 months prior to registration. 9. Active infection requiring intravenous systemic treatment. 10. HIV seropositivity. 11. Pregnant or breastfeeding women are excluded from this study (breastfeeding should be discontinued), because there is an unknown, but potential risk for adverse events in fetuses and nursing infants secondary to treatment of the mother with LMY-922 and lymphodepleting chemotherapy. Women of childbearing potential must have a negative serum pregnancy test 12. Serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive participants will be excluded.) 13. Participants with history of clinically relevant CNS pathology such as uncontrolled epilepsy, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia, and Parkinson's disease. 14. Participants with uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements. 15. Participants receiving a live vaccine within 2 weeks prior to screening. 16. Concurrent use of high dose systemic steroids and/or immunosuppressive therapies. 1. Steroid dose must be able to be weaned to 0.5 mg/kg/day or equivalent prior to CAR-T cell infusion. 2. Immunosuppressive medications must be able to be stopped at least 5 halflives prior to CAR-T cell infusion. 17. Treatment with rituximab or other B cell depleting agent within 6 months of planned CAR-T cell infusion, or treatment with agents such as etanercept, adalimumab, anakinra, infliximab, certolizumab pegol, belimumab, golimumab, abatacept, or tocilizumab within 4 weeks or 5 half-lives (whichever is shorter) prior to planned CAR-T cell infusion. 18. Participants with IgG levels \< 600mg/dL.