Safety and Efficacy of BAFF-R CART for Refractory Neuroimmune Diseases

To evaluate the DLT occurred within 3 months after BAFF-R CART cells infusion.

To evaluate the AEs occurred within 2 years after BAFF-R CART cells infusion.

The changes of concentration of soluble BAFF in the peripheral blood after BAFF-R CART cells infusion.

The changes of pathogenic antibody titers in peripheral blood or cerebrospinal fluid.

The changes of peripheral blood Neurofilament Light chain (NfL) concentration in patients with MS.

The number of BAFF-R CAR gene copies (VCN, copies/μg DNA) in peripheral blood and cerebrospinal fluid after administration.

The concentration of BAFF-R CAR T cells (cells/mL) in peripheral blood after administration was detected by flow cytometry.

The number of attacks divided by observed year after BAFF-R CART cells infusion.

the number of accumulate total active MRI lesions after BAFF-R CART cells 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 is a scale for assessing neurologic impairment in multiple sclerosis (MS). It 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 from MS). A negative change from baseline indicates improvement. A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more.

Modified Rankin Scale (mRS) is a profoundly valid and reliable measure of disability and is broadly utilized for assessing stroke outcomes and degree of disability. We characterized a favorable outcome as mRS ranging from zero up to two, while unfavorable outcome ranging for 3 up to 6.

Corrected visual acuity is determine by Snellen E chart held at a distance of 5 meters. Higher score indicates better vision.

The QMG score is a 13-item scale used to quantify disease severity in myasthenia gravis. The scale measures ocular, bulbar, respiratory, and limb function, grading each finding, and ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits).

The MG-ADL is an eight-question survey of symptom severity, with each response graded from 0 (normal) to 3 (most severe). Two questions concern ocular, three oropharyngeal, one respiratory, and two extremity functions. Cumulative MG-ADL scores range from 0 to 24.

The INCAT score comprises two parts, the arm score and the leg score. Based on a patient's level of impairment in their arms and legs, each part is scored between 0 and 5 points, resulting in an INCAT total score between 0 and 10.

The MRC score system for testing and grading of muscle function aims to provide a standardized and objective way to assess muscle function. It ranges from 0 to 5.

Including motor nerve distal latency, proximal latency, compound muscle motor potential (CMAP), motor nerve conduction velocity, sensory nerve conduction velocity, sural nerve potential.

For MMT score, 16 muscle groups/ motions will be tested (not individual muscles). 14 of these are tested bilaterally.

If the creatine kinase level drops to twice the upper limit of normal or below, it is defined as effective, and the effective rate is calculated.

Calculating the hyperintensity of muscle MRI T2/STIR sequence in patients with IMNM.

SF-36 will used to understand the health related quality-of -life of the subjects after BAFF-R CART cells infusion. The eight health concepts: limitations in physical activities because of health problems; limitations in social activities because of physical or emotional problems; limitations in usual role activities because of physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; vitality (energy and fatigue); and general health perceptions will be searched. These outcomes will be grouped as physical component summary and mental component summary. The norm data is 0-100, the health related quality of life is increases as the scores are increased. The average score is 50.

Health status is measured with the EuroQuality of Life Five Dimensions (EQ-5D) after BAFF-R CART cells infusion, which includes five dimensions and is used to evaluate the quality of life of sepsis survivors. They are mobility, self-care, usual activities, discomfort or pain and depression or anxiety. Levels are coded 1-5 and a total score is then generated. Results for the demographic measured will be displayed as a percentage value.

usual visual analog scale (VAS) of pain is used to evaluate pain after BAFF-R CART cells infusion (line from 0: no pain to 10:worst pain).

The number of In-patient hospitalization is defined as a stay in hospital that goes beyond midnight of the first day of admission.

Changes of concentration( pg/mL) of cytokines ( such as ferritin, CRP, IL-6 and procalcitonin) will be analyzed after Changes of concentration( pg/mL) of cytokines ( such as ferritin, CRP, IL-6 and procalcitonin) will be analyzed after BAFF-R CART cells infusion.

Anti-drug antibodies (ADA) against CAR on BAFF-R CART cells will be analyzed after BAFF-R CART cells infusion.

Levels of replication competent lentivirus (RCL) will be monitored after BAFF-R CART cells infusion.

Changes in cells in infused CART products, blood and CSF (including proportion of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells, ratio of CD4+ T/CD8+T, and single-cell sequencing) will be analyzed after BAFF-R CART cells infusion.

Annualized relapse rate (ARR): Number of MS relapses divided by observed year after BAFF-R CART cells infusion.

Time from BAFF-R CART cells infusion to the first relapse of MS.

The changes of enhancing Lesions as detected by brain Magnetic Resonance Imaging (MRI).

Annualized rate of T2 lesions：Number of New, and/or Enlarging T2 Hyperintense Lesions as detected by MRI divided by observed year after BAFF-R CART cells infusion.

The percent change of T2 lesions volume as detected by MRI from the baseline.

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 is a scale for assessing neurologic impairment in multiple sclerosis (MS).

The no evidence of disease activity-3 (NEDA-3), defined as no relapse, no disability worsening, and no MRI activity.

Time to onset of 3-month CDP as assessed by EDSS score.

Time to onset of 6-month CDP as assessed by EDSS score.

Including Fatigue Symptoms and Impacts Questionnaire -Relapsing Multiple Sclerosis (FSIQ-RMS), General Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire (PHQ-9), Health Utilities Index (HUI-III), Multiple Sclerosis Impact Scale (MSIS-29).