Manipulating immune regulation to improve the success of hematopoietic stem cell transplantation.

Funding Details
Canadian Institutes of Health Research
  • Grant type: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships (CGS-D)
  • Years: 2016/17 to 2017/18
  • Total Funding: $105,000
Keywords
Principle Investigator(s)
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Project Summary

For many blood cancer patients, hematopoietic stem cell transplantation (HSCT, also known as bone marrow transplantation) is the only option for a cure. HSCT works by replacing the patient's blood stem cells with new blood stem cells from a donor. The donated blood stem cells give rise to a new immune system, which can attack and kill the cancer cells in the patient. An unfortunate side effect occurs in up to 80% of HSCT patients when the new immune system attacks the patient's body, leading to a condition called graft-versus-host disease (GVHD). GVHD is a very serious complication that leads to death in about 1/3 of people who develop this side effect. My research aims to develop new ways to reduce the development of GVHD. I am studying how the powers of a type of immune cell, called a T regulatory cell (or Treg), which naturally prevents unwanted immune responses, can be harnessed for treatment of GVHD. In my first aim, I will study how a drug called anti-thymocyte globulin (ATG), which is used in HSCT, affects the development of Tregs. I will also test if there is an association between lower incidence of GVHD and more Tregs. This work will lead to a better understanding of how ATG can lower GVHD and also to new ways to monitor the presence of Tregs in HSCT. In my second aim I will develop a new way to modify Tregs so they can be used like a drug to prevent or treat GVHD. Specifically I will genetically engineer Tregs so their ability to suppress undesired immune responses is tailored for use in HSCT. This work will lay the foundation for a future clinical trial of genetically modified Tregs in HSCT and has applications for thousands of Canadians living with GVHD today.