CAR-T Cells Targeting Autoimmune Diseases

Autoimmune Diseases Clinical Trial

Official title:

CAR-T Cells Targeting B Cell Related Autoimmune Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05459870
• Other study ID #: GIMI-IRB-22010
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 31, 2022
• Est. completion date: June 30, 2026

Study information

• Verified date: July 2022
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: Lung-Ji Chang, PhD
• Phone: 86-0755-86725195
• Email: c[@]szgimi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 30, 2026
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. age older than 18 years.

2. expression of B cell surface molecules.

3. the KPS score over 80 points, and survival time is more than 3 months.

4. greater than Hgb 80 g/L.

5. no contraindications to blood cell collection.

Exclusion Criteria:

1. accompanied with other active diseases and difficult to assess treatment response.

2. bacterial, fungal, or viral infection, unable to control.

3. living with HIV.

4. active HBV or HCV infection.

5. pregnant and nursing mothers.

6. under systemic steroid treatment within a week of the treatment.

7. prior failed CAR-T treatment.

Related Conditions & MeSH terms

• Autoimmune Diseases

Intervention

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

Locations

Country	Name	City	State
China	Guilin Hospital of Chinese Traditional and Western Medicine	Guilin	Guangxi
China	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute	Guilin Hospital of Chinese Traditional and Western Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of 4SCAR T cells in patients with autoimmune diseases	Safety of 4SCAR T cells in patients with autoimmune diseases using CTCAE 5 standard to evaluate the level of adverse events	12 weeks
Secondary	B cell and immunoglobulin suppression activity of 4SCAR T cells in patients with autoimmune diseases	scale of CAR copies (for efficacy)	1 year
Secondary	B cell and immunoglobulin suppression activity of 4SCAR T cells in patients with autoimmune diseases	immunoglobulin levels (for efficacy)	1 year