GAD65-CAR treg cellular immunotherapy for type 1 diabetes
Adoptracell is developing antigen-specific chimeric antigen receptor regulatory T cell (CAR-Treg) therapies targeting GAD65 and other beta-cell autoantigens to reverse Type 1 Diabetes. Validated in a transgenic mouse model, the platform is advancing toward canine preclinical trials with potential applications across autoimmune diseases.
Overview
Adoptracell is pioneering a cellular immunotherapy approach for Type 1 Diabetes (T1D) using engineered regulatory T cells (Tregs) expressing chimeric antigen receptors (CARs) specific to pancreatic beta-cell autoantigens, with an initial focus on the GAD65 isoform. The therapy is designed to suppress diabetogenic effector T cells, restore immune tolerance, and promote islet regeneration and beta-cell recovery. By redirecting Treg specificity toward disease-driving antigens, the platform addresses a key limitation of current Treg therapies, namely the scarcity of antigen-specific cells and the safety concerns of broad immunosuppression.
Beyond T1D, the antigen-specific CAR-Treg platform has potential applicability to other autoimmune conditions where identified autoantigens drive disease pathology.
Technical specifications
Core technology:
- Engineering of Tregs with CARs derived from T1D patient autoantibody paratopes specific to GAD65 epitopes
- Expansion to additional beta-cell autoantigens including Insulinoma Associated Protein 2 (IA-2) and Preproinsulin
- Adoptive cell transfer of GAD65-CAR Tregs to suppress pancreatic inflammation and enable islet regeneration
Validation approach:
- In vitro effector T cell inactivation assays using T cells and pancreatic tissues from T1D-affected dogs, with cross-species comparison to mouse and human responses
- In vivo preclinical trial in four groups of GAD65 antibody-positive diabetic dogs comparing N-terminal and middle-region GAD65-CAR Tregs, unmodified Tregs, and EPCAM-CAR Tregs
- Pre-existing proof-of-concept data from a transgenic mouse model expressing human GAD65 and HLA-DQ8, in which GAD65-CAR Tregs reversed established spontaneous diabetes
Technology readiness level
The GAD65-CAR Treg program is at the preclinical stage. Proof-of-concept has been demonstrated in a transgenic mouse model showing reversal of established T1D, with observed improvements in blood glucose levels and insulin concentrations and a favorable safety profile. The current proposal extends validation into a canine T1D model, which represents a key translational step toward human clinical development. The program is supported by academic and state-level grants and is led by a team with expertise in gene and cell therapy.
About Adoptracell, INC.
AdopTracell, INC. is a preclinical-stage biotechnology company focused on the development of next-generation autoimmune therapies. The company specializes in the engineering of regulatory T cells (Tregs), utilizing chimeric antigen receptor (CAR) technology to improve immune tolerance. Their primary research efforts target Type 1 Diabetes (T1D) by developing GAD65-targeting CAR-Tregs designed to home to pancreatic islets, suppress diabetogenic T cells, and promote beta-cell recovery. The organization is led by a team of academic physicians and scientists with expertise in gene and cell therapy.
The company's work aims to address limitations in current Treg therapies, such as the low availability of antigen-specific cells, by creating targeted interventions that provide effective immune suppression without the adverse effects associated with broader immunotherapies. Preclinical studies have indicated that their GAD65-CAR-Treg approach can improve blood glucose levels and insulin concentrations while maintaining a favorable safety profile. AdopTracell’s development is supported by academic and state-level grants, reflecting its mission to transition fundamental research into clinical applications for autoimmune conditions.
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