CAR-T Cells Targeting Autoimmune Diseases

Sponsor

Shenzhen Geno-Immune Medical Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT05459870

Collaborator

Guilin Hospital of Chinese Traditional and Western Medicine (Other)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the feasibility, safety and efficacy of CAR-T cell therapy in patients with autoimmune disease. Another goal of the study is to learn more about the safety and function of the CAR-T cells and their persistency in autoimmune disease patients.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Diseases	Biological: 4SCAR T cells	Phase 1/Phase 2

Detailed Description

Autoimmune disease refers to the disease in which the immune system reacts to the host's own body and causes damage to tissues and organs. At present, the pathogenesis of various autoimmune diseases is still not well understood, but an imbalanced immune tolerance plays a key role in this process.

An ideal therapy to autoimmune disease should eradicate pathogenic autoimmune cells but retain the protective immunity. The chimeric antigen receptor-modified T (CAR-T) cell technology has proven to be highly effective in targeting B cell malignancies, and the treatment-induced B cell and antibody deficiencies have implications for treating autoantibody-related autoimmune diseases. Studies have shown that CAR-T cells targeting B cell surface molecules can kill autoreactive B lymphocytes in pemphigus vulgaris (PV) and systemic lupus erythematosus (SLE) patients. Thus, CAR-T cell technology targeting B cells has potential in treating autoimmune diseases including PV, SLE, autoimmune hemolytic anemia, Sjogren's syndrome etc..

CD19-specific CAR is based on activation of intracellular signalijng domains of T cells by the extracellular single chain variable fragment (scFv) antibody against CD19. The activated CAR-T cells can target and kill B cells. The investigation plans to use genetically modified T cells to express a 4th generation lentiviral anti-CD19 CAR with an inducible caspase 9 self-withdrawal gene (4SCAR) to increase the safety of this specific approach. Besides targeting CD19, specific CARs targeting other B cell surface molecules including BCMA, CD138, and BAFF-R will also be included in the treatment regimen. Based on accumulated experiences, the 4SCAR T cells have shown high safety profile without serious cytokine release syndrome (CRS) or neural toxicities in patients. Through this trial, the safety and long term efficacy of the B cell-specific 4SCAR T cell therapy will be evaluated, providing clinical evidence supporting the application of 4SCAR-T cell technology in the treatment of autoimmune diseases.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

CAR-T Cells Targeting B Cell Related Autoimmune Diseases

Anticipated Study Start Date :

Jul 31, 2022

Anticipated Primary Completion Date :

Jul 31, 2025

Anticipated Study Completion Date :

Jun 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4SCAR T Cell Therapy for autoimmune diseases	Biological: 4SCAR T cells Infusion of 4SCAR T cells at 10^6 cells/kg body weight via IV

Arm

Intervention/Treatment

Experimental: 4SCAR T Cell Therapy for autoimmune diseases

Biological: 4SCAR T cells

Infusion of 4SCAR T cells at 10^6 cells/kg body weight via IV

Outcome Measures

Primary Outcome Measures

Safety of 4SCAR T cells in patients with autoimmune diseases [12 weeks]
Safety of 4SCAR T cells in patients with autoimmune diseases using CTCAE 5 standard to evaluate the level of adverse events

Secondary Outcome Measures

B cell and immunoglobulin suppression activity of 4SCAR T cells in patients with autoimmune diseases [1 year]
scale of CAR copies (for efficacy)
B cell and immunoglobulin suppression activity of 4SCAR T cells in patients with autoimmune diseases [1 year]
immunoglobulin levels (for efficacy)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

age older than 18 years.
expression of B cell surface molecules.
the KPS score over 80 points, and survival time is more than 3 months.
greater than Hgb 80 g/L.
no contraindications to blood cell collection.

Exclusion Criteria:

accompanied with other active diseases and difficult to assess treatment response.
bacterial, fungal, or viral infection, unable to control.
living with HIV.
active HBV or HCV infection.
pregnant and nursing mothers.
under systemic steroid treatment within a week of the treatment.
prior failed CAR-T treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong	China	518000
2	Guilin Hospital of Chinese Traditional and Western Medicine	Guilin	Guangxi	China	541000