Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System

Inclusion Criteria:

1. Male or female subjects aged 18-75 years (including 18 and 75 years);

2. Subjects with Relapsing/refractory Antibody-mediated inflammatory diseases of thenervous system without effective treatment, including:

3. Subjects must be diagnosed as AQP4-IgG-positive NMOSD defined by 2015 criteriaof IPND NMOSD and meet the following requirements: i. At least one kind ofimmunosuppressant has been used for more than one year with poorly-controlledsymptoms; ii. Clinical evidence of at least two relapses in the last 12 monthsor three relapses in the last 24 months and one relapse in the preceding 12months before screening.

4. Subjects with MG with positive abnormal antibody, MG-ADL total score ≥ 6points, MGFA classification II-IV defined by 2020 MGFA diagnostic criteria andmeet the following requirement: i. At least one kind of immunosuppressant forstandardized treatment for more than 1 year, and have one of the following poorcontrol conditions: 1) continuous inability to affect daily life; 2)Exacerbation of MG symptoms and/or crisis attacks still occur despite standardtreatment; 3) Inability to tolerate immunosuppressive therapy ii. Requiresplasma exchange or maintenance therapy with IV gamma globulin

5. Subjects with CIDP with positive abnormal antibodies, INCAT disability scalewith total score of 2-9 defined by 2021 EAN/PNS diagnostic criteria and meetthe following requirement: i. Standardized use of at least one first-linetherapy for more than 3 months (cortisol hormone therapy, gamma globulin orplasma exchange therapy) with poorly-controlled symptoms. ii. Inability totolerate cortisol hormones, gamma globulin, and plasmapheresis because of sideeffects or other conditions

6. Subjects were diagnosed with IIM defined by 2017 European League againstRheumatism/American Rheumatology (EULAR/ACR) conference Class criteria; Atleast one kind of cardiac enzymes (CK, AST, ALT, ALD, LDH) ≥1.5×ULN during thescreening period, or Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) ≥6, or at least one other sign of active disease within the last 6months: MRI, EMG, or muscle biopsy; positive serological tests formyositis-specific antibodies (MSA) or myositis-associated autoantibodies (MAA),or antinuclear antibody (ANA). and meet one of the following requirements: i. After at least 1 month of corticosteroid therapy and standardized use of at leastone immunosuppressant/modulator (eg, azathioprine, methotrexate, mycophenolatemofetil, cyclosporine, tacrolimus, Cyclophosphamide, leflunomide, intravenous gammaglobulin, etc.) for more than 3 months with poorly-controlled symptoms. ii. ii. Inability to tolerate the above traditional regimens due to side effects orother conditions; e. Subjects were diagnosed with PMS (including PPMS and SPMS) or RMS according tothe 2017 revision of the McDonald diagnostic criteria；EDSS score between 2 to 7points inclusive, at screening. Subjects with RMS should meet one of the followingrequirements after standard therapy: i. at least two relapses in the last two yearsbefore screening. ii. at least one relapse in the last one year before screening.iii. positive Gd-enhancing MRI in the last one year before screening. f. Subjects were diagnosed with POEMS syndrome according to the 2021 revised IMWGdiagnostic criteria and meet all of the following requirements: i. bone marrowinvolvement; ii. no response to traditional regimens treatment includingcorticosteroid, chemotherapy, protease inhibitor or inability to tolerate the abovetraditional regimens; iii. Have measurable lesions (refer to the 2021 revised IMWGstandard) iv. VEGF > 2 ULN; v. ECOG score ≥1; vi. ONLS score ≥1. g. Subjects were diagnosed with autoimmune encephalitis according to the 2016International Diagnostic Criteria for Autoimmune Encephalitis and meet all of thefollowing requirements: i. at least one pathogenic antibody positive; ii. previouslystandardized use of corticosteroid, at least one immunosuppressant/modulator,including CD20 monoclonal antibody with poorly-controlled symptoms or intolerance;iii. onset of autoimmune encephalitis within 3 months prior to screening; iv. mRSScore ≥2 or CASE score ≥4. h. Subjects were diagnosed with MOGAD according to the 2023 International MOGADDiagnostic criteria and meet all of the following requirements: i. a documentedpositive serum MOG Ab test using a cell-based assay (CBA); ii mRS Score ≥2; iiipreviously standardized use of corticosteroid, at least oneimmunosuppressant/modulator, including CD20 monoclonal antibody withpoorly-controlled symptoms or intolerance.

7. All acute toxic reactions resolved to baseline or ≤ grade 1 assessed using NCI-CTCAEv5.0 except the ones adjudicated by the investigator to pose no risks on subjects.

8. Enrolled subjects must have satisfactory organ function and laboratory findings asdefined by the following:i. Blood tests: absolute neutrophil count ≥ 2×109/L (ornormal lower limit set by the central lab of the institution), platelets ≥ 100 × 109/L, and hemoglobin ≥ 100 g/L; ii. Liver function: total serum bilirubin, alanineaminotransferase (ALT) and aspartate aminotransferase (AST) must be ≤ 1.5x theinstitutional normal upper limit (ULN); iii. Kidney function: CrCl ≥ 60ml/min/1.73m2 (according to the following Cockcroft-Gault formula); iv.Electrolytes: blood potassium ≥ 3.0 mmol/L; blood calcium ≥ 2.0 mmol/L, bloodmagnesium ≥ 0.5 mmol/L; v. Coagulation function: fibrinogen ≥ 1.0 g/L; APTT ≤ ULN + 10s; PT ≤ ULN + 3s.

9. Blood oxygen saturation > 91% in resting state.

10. Echocardiography suggests LVEF≥ 50%.

11. Expected life expectancy ≥ 12 weeks as assessed by the investigator.

12. After signing the informed consent form, subjects and their partners must be willingto use effective and reliable method of contraception, devices or medicines, withinone year after CT103A cells infusion (excluding contraception safety periods).

13. Subjects must provide written informed consent before the study begin.

Exclusion Criteria:

1. Patients do not have adequate mononuclear cells without mobilization for CAR-T cellmanufacturing.

2. History of autoimmune hemolytic disease.

3. History of solid organ transplantation.

4. Patients were treated with alemtuzumab within 6 months prior to apheresis. Patientswere treated with fludarabine or cladribine within 3 months prior to apheresis.

5. Patients with Papovaviruses infection.

6. Patients have been diagnosed with malignancies in the last 2 years prior toscreening except for non-melanoma skin cancer, stage I cancers with completeresection and low risk of relapse, localized prostate cancer post-treatments,biopsy-confirmed in situ cervical cancer, or squamous epithelial lesion by PAPsmear.

7. Chronic and active hepatitis B (HBV), hepatitis C (HCV), Human ImmunodeficiencyVirus (HIV) infection, CMV or syphilis infections concurrently.

8. MG crisis was not effectively controlled within 2 weeks before enrollment.

9. Known history of primary immunodeficiency (innate or acquired).

10. Patients with severe impaired cardiac function, including but not limited to thefollowing: unstable angina, myocardial infarction (within 6 months beforeenrollment), congestive heart failure (≥Grade III by NYHA), severe ventriculararrhythmia.

11. Cerebrovascular accidents, including transient ischemic attack or stroke history,occurred within 6 months before enrollment.

12. Major operation or surgical treatment caused by any reason within 4 weeks beforeenrollment.

13. Any serious and/or uncontrolled comorbidities which may interfere with theevaluation during the study in the opinion of the investigator

14. Previous treatments: History of thymectomy within 12 months prior to CT103Ainfusion;

15. History of psychoactive drug abuse and failed to withdraw, or have a history ofpsychiatric disorders.

16. Prone to allergies or history of serious allergy.

17. Pregnant or lactating women.

18. Patients with other conditions adjudicated by the investigator as unsuitable forenrollment.

Criteria for lymphodepletion and CAR-T cells infusion:

Before lymphocyte depletion and CAR-T cells infusion, patients are evaluated and those meeting the following criteria cannot be included:

1. Blood tests: neutrophil count < 2 × 109/L, platelet count < 50 × 10^9/L;

2. Oxygen inhalation is required to maintain blood oxygen saturation ≥ 91%;

3. Patients have the following conditions, including but not limited to: new arrhythmiacannot be controlled by drugs; hypotension requiring pressor drugs; bacterial,fungal or viral infection requiring intravenous antibiotic treatment; creatinineclearance rate < 50 ml/min ;

4. Patients require maintenance support treatment within one week to meet the criteriafor lymphodepletion or CAR T cell infusion.

5. Cell infusion is delayed > 7 days after lymphodepletion for any reason;

6. Patients with other conditions adjudicated by the investigator as unsuitable forlymphodepletion or cell infusion.