You are here

A chimeric protein for the selective expansion of regulatory T cells

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI125039-01
Agency Tracking Number: R41AI125039
Amount: $260,665.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA15-270
Timeline
Solicitation Year: 2016
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-03-01
Award End Date (Contract End Date): 2017-08-31
Small Business Information
511 ST JOHNS CT
Oak Brook, IL 60523-2553
United States
DUNS: 079959173
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 BELLUR PRABHAKAR
 (312) 996-1831
 bprabhak@uic.edu
Business Contact
 BELLUR PRABHAKAR
Phone: (312) 659-0041
Email: bprabhak@gmail.com
Research Institution
N/A
Abstract

DESCRIPTION provided by applicant Type diabetes T D is a chronic disease caused by the autoimmune destruction of the insulin producing beta cells in the pancreas Current treatment options for T D are severely limited All patients diagnosed with T DM are placed on life long insulin therapy and the current standard of care for adult patients with T DM is intensive diabetes therapy to avoid long term medical complications such as diabetic nephropathy neuropathy and retinopathy among other complications T cells are believed to play a major role in the autoimmune destruction of pancreatic cells in T D Many aspects of immune regulation including regulatory T cell Treg function has been found to be defective in T D Hence restoration of Treg numbers and function to normalcy can be an effective strategy in preventing and or treating T D Several TCR activation dependent methods have been developed for Treg expansion but they cannot be used in vivo because such methods can activate Teff as well as Tregs thus limiting the therapeutic efficacy Methods for TCR dependent ex vivo Treg expansion have been developed but is impractical as the Tregs will have to be patient specific and requires repeated ex vivo expansion Our recent studies have shown that soluble OX L and Jagged Jag can cause a significant expansion of Tregs in vivo and suppress T D in NOD mice However developing a clinically acceptable therapeutic consisting of two soluble ligands may face regulatory hurdles We have developed mouse m and human h OX L Jag Fc fusion proteins that can be used to expand Tregs ex vivo In our Phase studies we will establish their therapeutic potential by testing their abilityto induce Tregs in vivo through the following aims In aim we will test if mOX L Jag Fc fusion protein can expand Tregs and delay prevent the onset of hyperglycemia in NOD mice In aim we will test if hOX L Jag Fc is able to expand human Tregs in immunodeficient NSG mice reconstituted with human immune cells Successful outcome of our studies would illustrate the potential clinical utility of our novel therapeutic Subsequently Absorption Distribution Metabolism Excretion and Toxicity studies can be carried out to establish the safety of OX L Jag Fc required for IND filing to FDA This novel therapeutic can be potentially used to effectively treat T D and other autoimmune diseases with Treg insufficiency

PUBLIC HEALTH RELEVANCE Type diabetes T D is a chronic disease caused by the autoimmune destruction of the insulin producing beta cells in the pancreas resulting in severe hyperglycemia Current treatment options for T DM are severely limited All patients diagnosed with T D are placed on life long insulin therapy and the adult patients are subjected additional therapy to avoid long term medical complications such as diabetic nephropathy neuropathy and retinopathy T cells play a major role in the autoimmune destruction of pancreatic cells in T D Many aspects of immune regulation especially regulatory T cell Treg function have been found to be defective in T D Hence restoration of Treg numbers and function to normalcy can be an effective strategy in preventing and or treating T D We have produced recombinant mouse mOX L Jag Fc and human hOX L Jag Fc chimeric proteins and successfully used them for the selective ex vivo expansion of mouse and human Tregs respectively In the current proposal we want to establish if treatment of NOD mice with the mOX L Jag Fc can cause Treg expansion and prevent delay onset of T D and humanized NSG mice with hOX L Jag Fc can cause human Treg expansion This novel therapeutic can be potentially used to effectively treat T D and other autoimmune diseases with Treg insufficiency

* Information listed above is at the time of submission. *

US Flag An Official Website of the United States Government