Autologous CD6-CAR Treg Cells for Patients With Stage 3 Type 1 Diabetes

Study Summary

Type 1 diabetes (T1D) is a persistent and gradually increasing genetic autoimmune disease requiring life-long management. The disease commonly impacts children. However, a quarter of cases are diagnosed in adults. The pancreatic islet beta-cells are responsible for producing insulin, a peptide hormone that is involved in the tight regulation of blood glucose levels. In T1D, the beta-cells are mistakenly destroyed by autoreactive T cells resulting in insulin deficiency and an inability to regulate blood glucose levels. The cause for such an autoimmune reaction to beta-cells is under active investigation. T regulatory cells (Tregs), are specialized immune cells that typically act to control your immune system. Tregs can be modified in the laboratory to recognize and deactivate T1D-causing cells. This process is done by inserting a piece of DNA (the molecules inside cells that carry genetic information and pass it from one generation to the next) into the Tregs. A non-infectious virus called a lentivirus will carry the piece of DNA into the cells that were collected from a donor. Tregs are then grown to large numbers in the laboratory and stored for treatment of T1D. It is not known whether these Tregs cells will treat T1D.

Primary Outcome

Toxicity will be graded according to the CTCAE version 65.0; cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) will be assessed per ASTCT consensus criteria \[8\]; Hyperglycemia/DKA will be graded per the Clinical Islet Transplant Consortium Terminology Criteria for Adverse Events (CIT-TCAE). Unacceptable toxicity (UT) and moderate toxicity (MOD) are defined in Section 11.2. All patients who are not evaluable for UT or MOD will be replaced.

Interventions

• DRUG AutoCD6-CAR Treg cells