Director: Jeffrey Bluestone
The mission of the JDRF COLLABORATIVE CENTER FOR CELL THERAPY at the University of California, San Francisco (UCSF), Columbia University (CU), La Jolla Institute for Allergy and Immunology (LIAI), Benaroya Institute (BI) and the University of Pennsylvania (UPenn) is to promote basic and clinical research that will lead to successful antigen-specific regulatory T cell therapy in patients with ongoing auto-aggressive Type 1 Diabetes.
The approach is multi-faceted taking advantage of the novel tolerogenic and autoantigen-specific properties of regulatory T cells pioneered by these research groups. The insights into the generation, expansion and functional characterization of regulatory T cells, combined with superb tools for conducting a successful clinical program will allow early proof of principle phase I/II trials using antigen-specific Tregs developed under cGMP conditions.
Description of Project
In an effort to take advantage of the current basic biology and move aggressively towards the first clinical trials in type 1 Diabetes, the following projects will be conducted:
- Project 1 (Bluestone) Expansion of Tregs for the treatment of autoimmune diabetes
- Project 2 (June) Second Generation APCs as stimuli of polyclonal and antigen-specific regulatory T cells
- Project 3 (Herold) Anti-CD3 plus antigen based induction of regulatory CD8+ T cells
- Project 4 (Ziegler) – Use of Foxp3 to induce and regulate antigen-specific Tregs
- In addition, the Center will support two pilot projects aimed at developing new approaches to regulatory cell therapy.
- Project 5 (Von Herrath) – Ag mechanism by which CD11c+DX5+ cells protect from diabetes
- Project 6 (Buckner) – Generation of Ag-specific Tregs from CD4+CD25- T cells using MHC-peptide tetramer
Finally, the center will support Cell Expansion Core; a Clinical Operations and Regulatory Affairs Core; and an Administrative Core. Together these projects will focus on rapid clinical application of the biology gleaned from the basic projects. Anticipated Outcome:
We anticipate that using novel and innovative tools, we will achieve robust expansion and functional integrity of Tregs and other suppressor cell populations for use in the treatment of Type 1 Diabetes.
Relevance to Type 1 Diabetes
Our studies are aimed at developing the wherewithal to expand regulatory cells from the limited sources available. Efficient expansion of functional Tregs in vitro would make relatively straightforward the routine therapeutic use of cell therapy for the treatment and prevention of Diabetes. It is believed that correct administration of novel immunotherapeutic agents will result in stable tolerance to leading to sustained insulin independence without associated procedural risks and drug toxicity.