• Reid, Gregor

    Titles
    Investigator, Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital
    Assistant Professor, Division of Hematology, Oncology and BMT, Department of Pediatrics, Faculty of Medicine, University of British Columbia
    Scientist, Michael Cuccione Childhood Cancer Research Program
    Degrees / Designations
    B.Sc., PhD
    Primary Area of Research
    Childhood Diseases
    Secondary Area(s) of Research
    Phone
    604-875-2000 ext. 4692
    Fax
    604-875-2373
    Lab Phone
    Mailing Address
    BC Children's Hospital Research Institute
    Room A5-162
    950 West 28th Avenue
    Vancouver, BC V6Z 4H4
    Affiliate Websites
    Research Areas
    Tumour immunology
    Summary
    The central idea of my research is that appropriate stimulation of the immune system will provide an effective strategy for the treatment and prevention of childhood cancers. Our research, therefore, seeks to understand the influence of the immune system during cancer progression and to use this knowledge to develop approaches to induce therapeutic anti-cancer immune activity. In addition to evaluating the impact of immune responses on established disease, our research seeks to identify the influence of the immune system before cancer is detected. To achieve these goals we use a range of experimental systems, including transgenic mice, adoptive transfer models, human xenograft models, and ex vivo and in vitro analysis of patient samples and human cell lines. It is hoped this broad approach will expedite the development of effective new treatments for children with cancer.
    Current Projects

    1. Immune therapy for acute lymphoblastic leukemia (ALL). This research addresses the issue of ALL immunogenicity and the induction of anti-ALL immune activity as a strategy to eradicate residual disease after chemotherapy. Our work has described the ability of immunostimulatory DNA (CpG ODN) treatment both to enhance the immunogenicity of primary human ALL blasts and to stimulate significant anti-ALL immune activity resulting in T cell-mediated protection against disease progression. This work provided the first report of immune-mediated killing of primary human ALL in vivo in the absence of adoptive transfer of lymphocytes or stem cell transplantation, and indicates that toll-like receptor signaling may provide a clinically feasible strategy for augmenting immune responses against ALL. A clinical trial based on this approach is aboout to commence. The next major step in our development of CpG ODN as an immune therapy for ALL will involve the examination of their ability to induce anti-leukemia immune activity after chemotherapy in a spontaneous mouse model of ALL, and to generate ALL-specific T cells against autologous leukemia blasts from patients. By using such models, in which immune tolerance must be overcome, this ongoing work will be the most stringent pre-clinical testing yet of an immune therapy for pediatric leukemia. The goal of these studies is to provide insights that will optimize the clinical application of this approach.

    2. Immune influence on ALL development. Infection has long been postulated to play a role in the progression of childhood ALL. Using novel models of this disease we are actively identifying the influence of the immune system during a pre-leukemic state on the onset of ALL. Our research indicates that the immune system may exert considerable control over early pre-leukemic cell expansion, but other mechanisms, such as growth factor availability, may also be important. Our long-term goal is to identify the growth constraints on pre-leukemic expansion, understand the influence of infection on these constraints, and use this knowledge to develop targeted strategies to reduce the incidence of primary disease and relapse.

    Selected Publications

    Fujii H, Trudeau JD, Teachey DT, Fish JD, Grupp SA, Schultz KR, and Reid GS. (2007) In vivo control of acute lymphoblastic leukemia by immunostimulatory CpG oligonucleotides. Blood 109(5):2008-13. PMID 17068155

    Seif AE, Barrett D, Milone M, Brown VI, Grupp SA and Reid GS. (2009) Long-term protection from syngeneic acute lymphoblastic leukemia by CpG ODN-mediated stimulation of innate and adaptive immune responses. Blood. 114(12):2459-66. PMID: 19636062

    Barrett DM, Seif AE, Carpenito C, Teachey DT, Fish JD, June CH, Grupp SA, and Reid GS. (2011) Non-invasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for pre-clinical modeling. Blood 118(15):e112-7. PMID: 21856863

    Rolf N, Kariminia A, Ivison S, *Reid GS, and *Schultz KR (2015). Heterodimer-specific TLR2 stimulation results in divergent functional outcomes in B-cell precursor acute lymphoblastic leukemia. European Journal of Immunology 45(7):1980-90. PMID: 25867213 *denotes co-senior authors.

    Fidanza M, Seif AE, DeMicco A, Rolf N, Jo S, Yin B, Li Y, Barrett DM, Duque-Afonso J, Cleary ML, Bassing CH, Grupp SA, Reid GS. (2016) Inhibition of precursor B-cell malignancy progression by toll-like receptor ligand-induced immune responses. Leukemia 30(10): 2116-2119. PMID: 27220664

    Fidanza M, Seif AE, Jo S, Kariminia A, Rolf N, Sly LM, Grupp SA, Reid GS. (2017) IFN-γ directly inhibits murine B-cell precursor leukemia-initiating cell proliferation early in life. European Journal of Immunology 47(5):892-899. PMID: 28295300

    Jo S, Lee JH, Mattei JJ, Barrett DM, Grupp SA, *Reid GS, and *Seif AE. (2017) Epitope spreading is required for long-term protection against acute lymphoblastic leukemia. Leukemia. September 2017; doi: 10.1038/leu.2017.290. PMID: 28924244  *denotes co-senior authors

    Rolf  N, Smolen KK, Kariminia A, Velenosi A, Fidanza M, Strahlendorf  C, Seif AE, and Reid GS. (2017) Correlation of distinct immune cell compartments with end of induction absolute lymphocyte counts for pediatric B cell precursor acute lymphoblastic leukemia. Cancer Immunology, Immunotherapy. doi: 10.1007/s00262-017-2070-3. PMID: 29052781

    Grants
    • Canadian Institutes of Health Research
    • Canadian Cancer Society
    • Leukemia & Lymphoma Society of Canada
    Honours & Awards
    Research Group Members
    • Dr. Arnawaz Bashir - Technician
    • Dr. Nina Rolf - Postdoctoral Fellow
    • Sumin Jo - Doctoral Student
    • Reza Rahavi - Doctoral Student
    • Matthew Gynn - Master's Student