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 will be 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 will test whether the immunogenicity of actionable candidates can be enhanced using phosphatase inhibitors (PI).

Expected Achievements/Impact: The ultimate objective of the project is to use TSAs to create precision therapeutic vaccines against AML and ALL. While having minimal (if any) side effects, those vaccines would represent a major breakthrough in leukemia treatment and would pave the way to the development of similar vaccines for other types of cancer. It is also fair to say that cancer vaccines may represent one the most cost-effective way to save lives. In addition, a major advantage of TSAs over classical drug targets is that TSAs are directly actionable (as components of therapeutic vaccines), bypassing many phases of the long and very costly drug development process.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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

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