MON-LB033 Unleashing the Anti-Inflammatory Potential of Treg Cells Against Type I Diabetes Using Advanced Chimeric Antigen Receptor Technology

• DOI: 10.1210/js.2019-mon-lb033
• Publication Date: 2019-05-10T01:41:12Z
• Authors: Shahnawaz Imam; Juan Jaume
• Keywords: Regulatory T cell; Adoptive Cell Transfer

Regulatory T (Treg) cells play a critical role in maintenance of tolerance and are ideal for development therapies designed to suppress inflammation autoimmunity. Emerging data indicate that, compared polyclonal Tregs, adoptive transfer disease-relevant antigen-specific Tregs is advantageous terms reduced risk nonspecific immune suppression need fewer cells. The successful use chimeric antigen receptor (CARs) technology the generation effector suggests that similar approach can be used generate Tregs. Here, we aimed at developing pancreatic Beta cell-specific CAR explore their therapeutic application against Type 1 diabetes (T1D). Methods: Two GAD65 B cell epitopes known interact with two immunodominant regions N-terminal (CAR-N), Middle (CAR-M) were selected assembly onto receptors (1). These prevent/treat our humanized mouse model closely resembles human T1D (2). Autologous, amplified transduced CAR-M CAR-N Treg constructs. expression CAR-M/N was confirmed by PCR western blot. First, group mice infused 5 million specific co-expressing GFP, 24 hr before sacrifice. then processed into single suspensions tracked peripheral blood, pancreas (PN), peri-pancreatic lymph nodes (PLN), spleen using flow cytometry. Also, 3D iDISCO image collected from same sites visualization post-infusion. Second, three groups treated either or untreated (normal control) EPCAM (CAR control). euthanized 30 days after treatment. Again, PN, PLN, spleens glucose tests (GTT) carried out infusion days. Results: homed islets hours infusion. population also significantly increased PN as GTT showed had lower blood 60 min being controls. 90 120 time points Untreated no significant differences EPCAM. Conclusion: results demonstrated potential potent, functional, stable humans. This project sets stage making treat other autoimmune diseases. 1) U.S. Provisional Patent #62/757,313 2) #62/713,827 Unless otherwise noted, all abstracts presented ENDO embargoed until date presentation. For oral presentations, session begins. Abstracts news conference conference. Endocrine Society reserves right lift embargo on promotion prior during ENDO.