Generation of a Multi-Antigen-Directed Immune Response for Durable Control of Acute Lymphoblastic Leukemia
This week we profile a recent publication in Leukemia from the laboratory of Dr. Gregor Reid
(back row, middle) at the BC Children’s Hospital Research Institute.
Can you provide a brief overview of your lab’s current research focus?
The focus of my lab is understanding the immunology of childhood cancer. We approach this research from two sides, asking both basic biology questions using mouse models and more translational questions using samples obtained from patients. The overall aim of this work is to identify the immune mechanisms that exert control over childhood cancer progression at various stages of disease and to use these insights to design more effective immune-based therapies.
What is the significance of the findings in this publication?
In this study we used a mouse model of acute lymphoblastic leukemia, the most common pediatric malignancy, to identify the components of an immune response that are necessary to achieve a long-lasting remission. We found that while a response directed against a single target antigen was able to exert early control over leukemia, it was not sufficient to sustain remission; prolonged survival required that the immune response spread to include other targets. In addition, we observed that achieving such a broader response may be challenging in children because some of the best potential targets occur very early in life and may, therefore, be hidden from the immune system.
What are the next steps for this research?
This finding has implications for single antigen-targeted immune therapies, such as CAR-T cells, and suggests that additional strategies may be required in children to generate the effective broad immune response. The study provides evidence to support the development of combination therapies, such as CAR-T with checkpoint blockade antibodies, in order to generate multi-targeted immune responses. In collaboration with Dr. Alix Seif’s group at The Children’s Hospital of Philadelphia, we will now investigate which therapeutic combinations achieve the strongest responses.
This research was funded by:
Leukemia & Lymphoma Society of Canada
Canadian Institutes of Health Research
American Cancer Society