Deadlines are 5:00 PM (Eastern). No extensions will be granted.
|Letter of Intent Required
|Dec 03, 2015
|Mar 02, 2016
|Jul 31, 2016
|Sep 30, 2016
Background & Purpose
JDRF is soliciting letters of intent (LOI) for the identification of key barriers in the way of therapeutically restoring immune tolerance in type 1 diabetes (T1D) after the onset of autoimmunity (i.e., in at-risk autoantibody positive pre-diabetic, recent-onset diabetic, and established disease subjects). Such efforts are intended to support the ultimate goal of identifying targets, combination therapies, and treatment strategies for T1D. JDRF is committed to translation of research findings towards clinical results and is most interested in projects that have clinical translation potential.
Because T1D results from a failure to maintain immune tolerance to pancreatic islet antigens, targeting the immune response to these autoantigens may provide a safe and effective means of preventing and controlling the autoimmune response while avoiding the harmful effects associated with non-specific immunosuppression. Immunotherapeutic approaches for preventing or halting T1D have involved both autoantigen-specific immunotherapies (ASIs) and non-autoantigen immunomodulatory (IM) interventions such as antibody therapeutics targeting pathogenic immune cell surface molecules and cytokines. While disease prevention or treatment trials with ASI or IM agents have not demonstrated robust, durable effects on immune tolerance or metabolic disease outcomes, such studies have provided compelling evidence of enhanced regulatory T (Treg) cell numbers and functions and reduced memory T effector (Teff) cell subsets, suggesting that immune tolerance might be achieved with the appropriate improvements to therapy. Because ASIs are expected to be a safe approach for restoring and maintaining immune tolerance, it is critical to understand the physiological conditions (and identify barriers) that allow for optimal ASI performance. Such barriers that adversely influence the capacity of ASIs to achieve tolerance include 1) the pathogenic immune/inflammatory environment driven by autoreactive Teff cells, 2) any functional defects of Treg cells relevant to T1D, 3) the specific antigenic component(s) of ASIs, and 4) specific therapeutic requirements of a defined disease stage or patient subpopulation. It is expected that many such barriers can be removed with combination therapies that “help” ASIs enhance regulatory cells and reduce pathogenic cells.