*CLAUDE PERREAULT

Identification of Tumor Specific Antigens to Develop Therapeutic Vaccines Against Acute Myeloid and Lymphoid Leukemias

Challenge: Acute myeloid and lymphoid leukemias (AML and ALL) are lethal hematologic cancers that affect both children and adults. Despite major progress in the treatment of pediatric AML and ALL, relapse and disease progression in patients with high-risk disease remain common problems. Furthermore, current drugs and radiotherapy treatments are associated with a wide array of long-term side effects. The idea that T-cell responses can induce remission of acute leukemias is now supported by several lines of evidence. This raises the possibility that tumor-specific antigens (TSAs) expressed in tumors could be identified and used to develop cancer vaccines. To date, such specific antigens have not been identified in leukemias.

Solution: In order to discover human TSAs, the team has developed a high-throughput approach allowing identification of TSAs derived from any types of genetic alterations, including TSAs expressed from allegedly non-coding regions of the genome (cryptic). Using this innovative method based on next-generation sequencing, mass spectrometry, and bioinformatics, the researchers were able to eliminate putative TSAs that are also expressed in normal cells, thus generating a repertoire of true tumor-specific antigens for human AML and ALL. In addition, the team evaluated whether the immunogenicity of actionable candidates can be enhanced using phosphatase inhibitors (PI).

Expected Achievements/Impact: The team identified 94 tumor antigens that represent attractive targets for acute leukemia immunotherapy. Many of them are able to stimulate the immune system and their expression in patients correlates with improved survival. Moreover, PI-treated dendritic cells have improved immune cell activation. Preventive vaccines against various pathogens represent the most cost-effective way to save lives. These findings should have a transformative impact on treatment of ALs. The results of this project also contributed to the creation of Epitopea, a spin off company that will be devoted to the development of TSA-based vaccines and of TSA-specific T-cell receptors for AML therapy.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigator:


Claude Perreault
Université de Montréal

Co-investigators

Pierre Thibault,
Sébastien Lemieux
Université de Montréal

Michel Tremblay
McGill University

Xavier Roucou
Université de Sherbrooke

Jean-Sébastien Delisle
Centre de recherche de
l’Hôpital Maisonneuve-
Rosemont

Completed Project
$ 1,500,000 / 3 years
Supported by CQDM through:
• MEIAnd by co-funding partners:
• Oncopole
• Cancer Research Society