Project summary: Enabling Studies Program
DEVELOPING T CELLS THAT TARGET ANTIGENS SPECIFIC TO LYMPHOID CANCERS
October 1, 2015 to March 31, 2017
- This therapeutic approach involves isolating and propagating T cells that can recognize and attack specific antigens in blood cancers
- This is the first time a proteomic approach has been used to discover and validate MiHAs in human lymphoma and chronic lymphocytic leukemia (CLL)
- Success would lead to more consistent, more effective and safer treatment of blood cancers compared to allogeneic transplantation
ABOUT THE PROJECT
In Canada, approximately half of the 16,000 people diagnosed with hematologic cancers (HCs) every year develop resistance to chemotherapy and die, representing an estimated 60,000 years of potential life lost.
For these patients, allogeneic hematopoietic cell transplantation (AHCT) is the sole curative treatment. However, there are two major problems with traditional ACHT: it has variable anti-cancer effects and comes with the risk of a devastating complication called graft-versus-host disease (GVHD), in which the donor cells attack the patient.
Research has shown that the curative effects of AHCT result from immune cells that are able to recognize and target the cancer cell’s minor histocompatibility antigens (MiHAs), which are small cell-surface proteins that function as signals for cells of the immune system. Preclinical and clinical studies suggest that the injection of T cells primed against a single MiHA can cure HCs without causing any GVHD.
The project team has identified 39 MiHAs expressed by hematopoietic cells using samples from 1,000 patients with hematologic cancers (e.g., non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL), but not acute leukemias). They want to identify and validate the best candidates for a clinical trial, and develop a protocol for submission the Health Canada.
Using T cells that target specific MiHAs has the potential to transform care for patients with blood cancers.
- Dr. Denis Claude Roy, Hôpital Maisonneuve-Rosemont, Université de Montréal
- Dr. Claude Perreault, Hôpital Maisonneuve-Rosemont, Université de Montréal
- Dr. Jean-Sebastien Delisle, Hôpital Maisonneuve-Rosemont, Université de Montréal
- Dr. Jonathan Bramson, McMaster University
- Dr. Raewyn Broady, BC Cancer Agency, University of British Columbia
- Dr. Andrew Daly, Tom Baker Cancer Centre, University of Calgary
- Dr. David Allan, The Ottawa Hospital, University of Ottawa
Keywords: adoptive cell therapy, minor histocompatibility antigens, MiHAs
Eligible cancers: chronic lymphocytic leukemia (CLL), lymphoid hematologic malignancies, non-Hodgkin’s lymphoma,
Partners: Cure: Blood Cancer, Hôpital Maisonneuve-Rosemont, Miltenyi Biotec