Manipulating immune regulation to improve the success of hematopoietic stem cell transplantation.
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
- CELLULAR THERAPY
- CHIMERIC ANTIGEN RECEPTOR
- GRAFT-VERSUS-HOST DISEASE
- health research
- HEMATOPOIETIC STEM CELL TRANSPLANT
- HY ANTIGEN
- IMMUNE RECONSTITUTION
- MASS CYTOMETRY
- REGULATORY T CELL
University of British Columbia
No researchers found.
No partner organizations found.
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.