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Diabetes and Vascular Disease

SUN-588 - GAD65-CAR-Tregs Home to Human Islets, Suppress Ctls and Reverse Type 1 Diabetes

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Shafiya Imtiaz Rafiqi, DVM, PhD: No financial relationships to disclose
Background
We have developed pancreatic beta-cell, antigen-specific, Chimeric Antigen Receptor (CAR) T regulatory cells (Tregs) and explored their therapeutic potential for type 1 diabetes (T1D)/Latent Autoimmune Diabetes of Adult (LADA) in human pancreatic tissues ex-vivo, and in a spontaneous humanized mouse model (T1D mice) in-vivo.
Results
Using live-cell imaging, we observed these Glutamic Acid Decarboxylase, 65 kD isoform (GAD65)-CAR-Tregs home to human pancreatic islets ex-vivo and proliferate upon encountering the cognate GAD65 antigen in the islets. Furthermore, human pancreatic-islet activated GAD65-CAR-Tregs also suppressed human T1D cytotoxic T lymphocytes (CTLs) in co-cultures (1). We confirmed these findings in-vivo, in a spontaneous humanized T1D mouse model (T1D mice) (2) by showing that mouse GAD65-CAR-Tregs also suppressed diabetogenic T responsive (Tresp) cells and were superior to normal Tregs. We also show that mouse GAD65-CAR-Tregs homed to mouse pancreatic islets in-vivo. Moreover, we conducted a 30-day pre-clinical trial in T1D mice, and observed normalization of fasting blood glucose, fasting insulin and glucose tolerance tests in GAD65-CAR-Treg treated T1D mice. We confirmed by histology, the advancement of Tregs, retreat of T effector cells in GAD65-CAR-Treg treated mice, that led to the recovery/reconstitution of pancreatic islets.
Discussion
Taken together, human GAD65-CAR-Tregs homed to human islets, suppressed diabetogenic T cells and when used to treat T1D mice that mimics human pathophysiology of T1D, GAD65-CAR-Tregs reversed T1D. Conceivably, treatment of T1D with GAD65-CAR-Tregs will allow for recovery/reconstitution of beta cells in human patients as well.
1. PATENT # WO2020097546 Antigen-specific chimeric antigen receptor Treg cells for prevention and/or treatment of autoimmune and alloimmune disorders.
2. PATENT # US20200037586 Transgenic C57BL6-BTBR mouse with a humanized MHC II gene that expresses GAD65.

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