CD38-Directed Immune Conditioning for Type 1 Diabetes

Current immunotherapies for Type 1 diabetes (T1D), such as anti-thymocyte globulin (ATG) and anti-CD3 monoclonal antibodies, have several limitations. While these agents broadly deplete T-cell populations, they fail to completely eradicate the pathogenic autoreactive T cells attacking insulin-secreting beta cells in the islets of Langerhans, and preserve the essential regulatory T cells (Tregs) that prevent autoimmunity. Consequently, these therapies offer only a brief delay in disease progression and carry a substantial off-target toxicity. Thus, an urgent unmet need remains for targeted immune-conditioning strategies that selectively clear pathogenic T cells while preserving overall protective immunity.

The Meyer lab at Stanford has developed a novel CD38-directed strategy to selectively eliminate pathogenic autoreactive T cells. This approach leverages the high expression of CD38 on diabetogenic effector/memory T and B cells relative to naive T cells and Tregs, allowing for the selective depletion of pathogenic T cells while preserving cell populations essential for long-term immune tolerance. Furthermore, this non-genotoxic strategy leverages CD38's ectoenzyme role in modulating local NAD/adenosine signaling and T-cell activation thresholds to dampen inflammatory signaling in the pancreatic islets, thereby creating a temporary window in which other tolerance-inducing interventions can also be applied.

Stage of Research
Pre-clinical stage, in vivo data