The Kidney Foundation of Canada

Dr. Caroline Lamarche 

Dr. Caroline Lamarche

University of British Columbia, British Columbia
Supervisor(s):  Dr. Megan Levings

Tailoring antigen-specific regulatory T cells for use in transplantation


2017-2020:  $195,000  |  KRESCENT Post-Doctoral Fellowships  |  Category: Transplantation

Biography

Dr. Lamarche will complete her post-doctoral fellowship under the supervision of Dr Megan Levings at BC Children Hospital/University of British Colombia where she will work on a way to tailor antigen-specific regulatory T cells for their use in transplantation.

The success of transplantation has significantly improved due to the availability of better immunosuppressive drugs. However, heavier immunosuppression comes at the cost of an increased risk of infection and neoplasia. New ways to educate the immune system to tolerate transplanted organs are needed. One strategy is to harness the natural immunosuppressive properties of T regulatory cells (Tregs). In the last 10 years, research has shown that Tregs can be used as a cell-based therapy to induce immune tolerance and prevent organ rejection. The potency and specificity of Treg cell therapies is significantly enhanced if the cells are enriched for those that have a T cell receptor (TCR) that is specific for a disease-relevant antigen (i.e. antigen-specific cells). However, it’s hard to obtain enough of those cells to use in transplant recipients. Dr. Levings’ lab developed a method to improve the potency of Tregs by engineering them to express a chimeric antigen receptor (CAR) specific for a transplant-relevant antigen: HLA-A2. Dr. Lamarche will study the potential of A2-CAR Tregs to control allograft rejection and induce long-term transplant tolerance.

Lay Summary

Transplantation is the best and sometimes only treatment for end-stage organ failure. In the last ten years, the lives of more than 20,000 Canadians have been improved, extended, or saved by donated organs. lmmunosuppressive drugs make transplantation possible, but since these drugs cannot suppress just the cells reactive to the transplanted organ but suppress the entire immune system, these drugs come at the price of an increase in infection and cancer risk. The drugs are also not perfect; many organs are still lost to rejection.

Our goal is to improve the success of transplantation, by finding ways to re-educate the recipient's immune system to tolerate the transplanted organ. Our strategy is to harness the natural immunosuppressive properties of a type of white blood cell called T regulatory cells (Tregs). Tregs naturally regulate immune responses by ensuring the immune system attacks infectious or harmful substances without over-reacting to self or non-harmful foreign proteins. In the last 10 years, research has shown that Tregs could be used as a cell-based therapy to induce immune tolerance and prevent organ rejection. The efficacy of Treg cell therapies can be significantly enhanced if the cellular product is enriched for Tregs that recognize a target that is specific to the transplanted organ.

Dr. Levings' lab developed a method to improve the potency of Tregs by engineering them to express a protein that activates them when they are in the presence of a transplant. My goal is thus to study the potential of those engineered Tregs to control allograft rejection and lower the chances that transplant recipients will reject the donor organ.