CAR-T Cells Targeting Autoimmune Diseases

CAR-T Cells Targeting B Cell Related Autoimmune Diseases

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.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases
• Intervention / Treatment: Biological: 4SCAR T cells

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute
  • Guangxi
    • Guilin, Guangxi, China, 541000
      • Recruiting
      • Guilin Hospital of Chinese Traditional and Western Medicine
      • Contact: Qiyong Zhu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
B cell and immunoglobulin suppression activity of 4SCAR T cells in patients with autoimmune diseases	scale of CAR copies (for efficacy)	1 year
B cell and immunoglobulin suppression activity of 4SCAR T cells in patients with autoimmune diseases	immunoglobulin levels (for efficacy)	1 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborators: Guilin Hospital of Chinese Traditional and Western Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): July 31, 2022
• Primary Completion (Anticipated): July 31, 2025
• Study Completion (Anticipated): June 30, 2026

Study Registration Dates

• First Submitted: July 12, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 17, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: CAR-T; CD19; autoimmune disease; BCMA; autoantibody; CD138; BAFF-R
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: GIMI-IRB-22010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No