A Novel Therapy for Inflammatory Bowel Disease-Dual Regulatory T-Cell Programming
Abstract
Concept: This proposal describes an innovative strategy that is primarily intended for therapy of the inflammatory bowel diseases (IBDs). However, it can be potentially used for prevention of the diseases as well. The concept underlying this strategy is conceived in response to the problems associated with current clinical regimens for IBD treatment, e.g., increasing rates of infections and cancers. These problems are mainly caused by non-discriminating suppression of patients immunity. To circumvent the problems, this novel strategy will deliver two new drugs specifically into our immune system such that (1) one drug will instruct the immune system to increase production of a specialized immune cell subset, i.e., regulatory T cells (or Tregs) and (2) the other drug will guide the newly generated Tregs specifically into the troubled gut. The rationale behind this strategy is that the Tregs are potent immune suppressors and can selectively migrate into the gut if appropriately instructed. We expect that these newly arrived Tregs in the gut will halt the colitis without compromising general immunity. In this regard, a significant innovation in our strategy is its potential to augment numbers and functions of the Tregs in the gut, but this augmentation will not affect the ability of our immune system to fight against infections and cancers. This study aligns with the Fiscal Year 2014 Peer Reviewed Medical Research Program topic area of inflammatory bowel disease. Critical Problems to Be Addressed: The critical problem to be addressed is suppression of colitis exclusively in the gut such that a patient s general immunity will not be compromised. This is crucial because a diminishing ability of the immune system to fight against infections and cancers has been a well-recognized problem during treatment of IBD patients especially children using currently available clinical regimens. Since a perpetual immune response in the gut is a major mechanism that causes the chronic colitis in the gut of an IBD patient, our strategy, which will instruct our immune system to increase production of the Tregs and subsequently guide the newly generated Tregs specifically into the troubled gut, can potentially solve this problem. Innovations: Although various strategies especially Treg-based strategies are being intensively investigated, concerns such as instability of the Tregs generated by current methods has prevented smooth transition of preclinical studies to clinical applications. In this regard, our novel strategy will utilize a different method to generate stable Tregs in the immune system of a patient s body and subsequently "send" the newly generated Tregs into the troubled gut. This novel method may therefore overcome the instability issue. Our novel strategy will "send" the drugs only to the immune system. Therefore, the detrimental effects associated with current therapies as a result of systemically increased levels of these drug can be avoided. This strategy will for the first time test a potential to combine the beneficial effects of two drugs: one can stably increase production of the Tregs and the other can guide the newly generated Tregs specifically into the troubled gut in an IBD patient. Benefits for Military Personnel and Veterans: The continuously increasing prevalence of IBDs among Veterans in the United States necessitates an improved nonsurgical therapy for these IBD patients. Furthermore, active military service especially combat field service may predispose Soldiers to subsequent development of IBDs. A modality for preventing subsequent development of IBDs among active military Service members can be beneficial. The strategy described here may be utilized for both therapeutic and preventive purposes. Ultimate Application: The ultimate application of this proposed strategy will be twofold, one is therapy and the other is prevention. Therefore, if the strategy is successfully tested,
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510240
Entities
People
- Xiaolei Tang
Organizations
- Loma Linda University
- United States Army