|A Potential T Cell Therapy Clears Laboratory Hurdles|
|Martedì 30 Giugno 2009 22:37|
JDRF-funded researchers have discovered further evidence that regulatory T cells are a promising cell-based therapy for type 1 diabetes. Jeffrey Bluestone, Ph.D., and colleagues from the Diabetes Center at the University of California, San Francisco have shown that regulatory T cells can be isolated from people with type 1 diabetes, and then expanded in the laboratory to levels that could be therapeutically useful without a loss of function or stability.
The work was supported by a JDRF Collaborative Center for Cell Therapy Grant to Dr. Bluestone, and a postdoctoral fellowship award to researcher Todd Brusko.
Barry Jones, Ph.D., director of JDRF's autoimmunity program, said the study's solid pre-clinical results provide "clear mechanistic rationale" for a human clinical trial using regulatory T cells. A small phase I study, representing an initial assessment of the therapeutic benefits of such a therapy in people, is being planned.
The goal of the proposed therapy is to restore balance within the immune system by shifting immune system activity toward greater regulation and tolerance. Although the mechanism underlying this shift is not fully understood, there is strong and compelling evidence of the success of the approach in mice with diabetes. The transfer of regulatory T cells expanded in the laboratory somehow "can overcome intrinsic defects and restore tolerance in type 1 diabetes," the scientists said, emphasizing that early treatment would likely provide the best outcomes.
"The therapeutic benefits of restoring tolerance early in type 1 diabetes would likely result in the preservation of endogenous beta-cell mass and subsequent reduction in complications resulting from hyperglycemia."
Method of Regulatory T cell Expansion
Large Numbers of Cells Are Grown
Next Steps and Considerations
One of the strengths of the study is that the isolated and expanded cells represent a multitude of distinct regulatory T cell lines-each with a specific regulatory task. This aspect of the therapy, the researchers said, is a "necessary advancement" in the treatment of type 1 diabetes because it provides a broader, more encompassing assault against the T cells that are mediating the disease.
However, before regulatory T cells can be used as a cell therapy for type 1 diabetes, several questions must be addressed. These include how long the expanded cells will survive after they are transferred, where in the body they will reside, and whether they will retain their desired suppressive nature once transferred.
"This study outlines important tools and principles for translating [regulatory T cell] therapies into clinical treatments for patients with type 1 diabetes and other autoimmune disorders," the researchers concluded.