A firm believer in the synergy that comes with collaborative multicenter trials, I am active in cooperative group trials including Children's Oncology Group (COG) (vice-chair of the Cellular Therapy discipline), Pediatric Blood and Marrow Transplant Consortium (PBMTC), NCIC-C17 developmental therapeutics and transplant committees, Canadian Blood and Marrow Transplant Group (president 2018-2020), and the Pediatric Immunodeficiency Disorder network (PIDTC).
Our program is active in asking important questions in several important transplant/cellular therapy multicenter trials. The FORUM trial (institutional PI), being run in 30 countries, is asking whether we can avoid total body irradiation as part of the transplant process for children with acute lymphoblastic leukemia; potentially sparing long-term side effects. We have several chimeric antigen receptor T cell trials open at SickKids evaluating their impact on the control of leukemia in children who have high-risk acute lymphoblastic leukemia. Additionally, early phase trials in gene therapy utilizing CRISPR/Cas9 editing of hematopoietic stem cells to correct/ameliorate thalassemia and sickle cell disease (institutional PI) are starting with a collaboration with hematologist colleagues.
We have many translational- and registry-based trials working towards making transplant/cell therapy more effective and less toxic.
Working in cellular therapy laboratory (GMP-compliant cell manufacturing) and related cord blood banking I have been active in the field of developmental cell therapeutics. My research focus has been on immune regulatory cells – myeloid derived suppressor cells and mesenchymal stem/stromal cells – both of which have potent abilities to modify the immune response. The laboratory, the Translational Transplant/Cellular Therapy Lab, supports clinical research projects and additionally has two main areas of research – better understanding of the role of inflammation in the early hematopoiesis peri-transplant and understanding the ontogeny of myeloid-derived suppressor cells. Myeloid-derived suppressor cells are a population of immature myeloid cells with profound suppressive functions that are able to shutdown T, B and dendritic cell function. We have found that these cells are enriched in allogeneic stem/progenitor cell grafts and recover early post-transplant, making them excellent candidates for modulators of the immune environment post-transplant both to prevent GVHD and enhance graft vs leukemia/tumor activity. Through a better understanding of the immunobiology of the graft and the early post-transplant setting we are looking at modifying immune function post-transplant to optimize anti-tumor responses in solid tumors such as neuroblastoma. A transplant/cell therapy biobank to support current and future studies is in development.