A Study of C-CAR168 in the Treatment of Central Nervous System Autoimmune Diseases Refractory to Standard Therapy

• CD20/BCMA-directed CAR-T cells (Biological), also known as C-CAR168: Autologous 2nd generation CD20/BCMA-directed CAR-T cells, single infusion intravenously

Primary outcomes

• Incidence and severity of Adverse Events [Safety and Tolerability] [Throughout the first 3 months follow up period completion]: Incidence and severity of adverse events (AE) and serious adverse events (SAE) within three months following infusion
• The subsequent recommended dose of C-CAR168 in patients with central nervous system autoimmune diseases refractory to standard therapy [Throughout the first 24 months follow up period completion]: Based on the assessment of overall safety profile

Secondary outcomes

• Incidence and severity of adverse events (AE) [Throughout the first 24 months follow up period completion]: Incidence and severity of adverse events (AE) and serious adverse events (SAE) during the study
• MS: No Evidence of Disease Activity-3 (NEDA-3) [Throughout the first 24 months follow up period completion]: Proportion of participants achieving NEDA-3 at 6 months post-infusion and during the study period
• MS and NMOSD: Expanded Disability Status Scale (EDSS) [Throughout the first 24 months follow up period completion]: Change from baseline in EDSS at 6 months and 24 months post-infusion. EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death).
• MS and NMOSD: MRI [Throughout the first 24 months follow up period completion]: Number of T1 gadolinium-enhancing lesions and new or enlarging T2 lesions, as well as their change from baseline, at 6 months and 24 months post-infusion. Change from baseline in total T2 lesion volume, gray matter volume (GMV), white matter volume (WMV), and brain volume (BV), as well as annualized-brain volume loss (a-BVL), at 6 months and 24 months post-infusion
• Autoimmune Encephalitis (AiE): Clinical Assessment Scale in Autoimmune Encephalitis (CASE) [Throughout the first 24 months follow up period completion]: Change from baseline in CASE at 6 months and 24 months post-infusion. The Clinical Assessment Scale in Autoimmune Encephalitis (CASE) has a score range from 0 to 27, and higher scores indicate a worse clinical outcome.
• MS, NMOSD and AiE: Annualized Relapse Rate (ARR) [Throughout the first 24 months follow up period completion]: ARR at 6 months and 24 months post-infusion
• Stiff-Person Syndrome (SPS): Distribution of Stiffness Index (DSI) [Throughout the first 24 months follow up period completion]: Change from baseline in DSI at 6 months and 24 months post-infusion. Distribution of Stiffness Index (DSI) is a validated indicator or stiffness. Scores range from 0 to 6 and reflect the extent of stiffness. Higher scores indicate a worse outcome.
• SPS: Heightened Sensitivity Score (HSS) [Throughout the first 24 months follow up period completion]: Change from baseline in HSS at 6 months and 24 months post-infusion. Heightened Sensitivity Score (HSS) measures changes in the frequency of spasms. Scores range from 0 to 7. Higher scores indicate a worse outcome.
• Pharmacokinetics (PK): Maximal plasma concentration (Cmax) [Throughout the first 24 months follow up period completion]: Cmax of C-CAR168 in peripheral blood
• PK: Time to reach the maximal plasma concentration (Tmax) [Throughout the first 24 months follow up period completion]: Tmax of C-CAR168 in peripheral blood
• PK: Duration in peripheral blood (Tlast) [Throughout the first 24 months follow up period completion]: Tlast of C-CAR168 in peripheral blood
• PK: Area under curve (AUC) [Throughout the first 24 months follow up period completion]: AUC of C-CAR168 in peripheral blood
• Pharmacodynamics (PD): Depletion of peripheral blood B cells, plasma cells, and CD20dim T cells [Throughout the first 24 months follow up period completion]
• PD: Decline of serum immunoglobulin [Throughout the first 24 months follow up period completion]

Other outcomes

• Serum cytokines changes [Throughout the first 24 months follow up period completion]: Detection of serum cytokines changes over time by flow cytometry
• Soluble BCMA changes in peripheral blood [Throughout the first 24 months follow up period completion]: Detection of soluble BCMA changes in peripheral blood by Enzyme Linked ImmunoSorbent Assay (ELISA)
• Changes in CSF CAR DNA copy number and CAR-T cells [Throughout the first 24 months follow up period completion]: Detection of changes in CSF CAR DNA copy number and CAR-T cells by quantitative polymerase chain reaction (qPCR) and flow cytometry

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

* 18 to 70 years old at the time of signing the Informed Consent Form (ICF).
* Diagnosed as Multiple Sclerosis (MS)/Neuromyelitis Optica Spectrum Disorders (NMOSD)/Autoimmune Encephalitis(AiE)/Stiff Person Spectrum Disorder(SPSD) according to recognized diagnostic criteria for at least 6 months.
* Prior treatment failure with standard therapy.
* Adequate bone marrow, coagulation, cardiopulmonary, liver and renal function.

Exclusion Criteria:

* Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Treponema Pallidum (TP) positive, Cytomegalovirus (CMV) DNA positive, Epstein-Barr Virus (EBV) DNA positive.
* Uncontrolled active infection.
* Live vaccine injection within 4 weeks prior to signing the ICF.
* Major organ transplantation history or bone marrow/hematopoietic stem cell transplantation history.
* Severe cardiovascular diseases within the past 6 months prior to screening.
* A history of ≥ Grade 2 bleeding within 4 weeks prior to screening, or requiring long-term anticoagulants treatment.
* Inadequate washing time for previous treatment.
* Previously treated with CAR-T cell products or genetically modified T cell therapies.
* Pregnant or lactating women.
* Severe central nervous system diseases or pathological changes.
* Malignancy history within 5 years prior to signing the ICF.
* Any contraindication to lumbar puncture.