Title: Development and Delivery of Inhibitors for Viral Pathogenic Deubiquitinases
In human viral diseases, misbehaviour of the cellular machinery utilizing ubiquitin is frequently observed. Ubiquitin is a small protein that attaches to target proteins in human cells and signals for their destruction. Human deubiquitinases are enzymes that remove ubiquitin to keep protein levels in balance. Viral pathogens have evolved proteins that mimic human deubiquitinases to evade the immune system by interfering with host ubiquitin-dependent processes. Unfortunately, the lack of molecules that can block the activity of viral deubiquitinases has severely hampered attempts to manipulate them for therapeutic benefits. We have invented a new technology to develop synthetic protein modulators for any ubiquitin-interacting proteins. The goal of this project is to generate highly specific and potent inhibitors for viral pathogenic deubiquitinases and a platform to deliver these molecules into human cells. This will lead to effective antiviral therapy, expanding the existing therapeutic portfolio of CCAB.
Title: Development of Cell-Based Functional Assays to Accelerate Commercialization and Therapeutic Application of Recombinant Antibodies
Antibodies are the fastest growing segment of the pharmaceutical market, and with modern engineering technologies antibodies can be programmed to target devastating diseases. Within the immune system, antibodies fight invading bacteria and viruses. High-quality synthetic antibodies directed to disease-related targets have immense therapeutic potential. Development of cell-based assays to enable rapid identification of functionally active antibodies is a critical step in the commercialization process. The proposed research project will involve screening of binders against disease-associated targets; antibodies showing clinical relevancy will be considered for entry into the clinical trial pipeline. The newly formed Centre for the Commercialization of Antibodies and Biologics (CCAB) will bridge the research and discovery occurring at the Donnelly Centre with industry partners to enable accelerated delivery of new therapies to fight diseases such as cancer, arthritis, and Crohn’s disease. CCAB will facilitate commercialization of antibodies by leveraging a world-class technology platform and experienced product development professionals.
Title: Targeting clonal heterogeneity in treatment-refractory glioblastoma with novel and empiric immunotherapies
Glioblastoma (GBM) is the most common primary adult brain tumor, characterized by extensive cellular and genetic heterogeneity. Even with surgery, standard chemotherapy, and radiation, tumor recurrence and patient relapse are inevitable with a median survival rate of <15 months. The overall goal of this proposal is to identify new therapeutic targets that drive clonal evolution in treatment-refractory GBM, develop novel and empirical immunotherapies that harness the immune system and target specific cell surface receptors on GBM cells at the same time, and undertake preclinical evaluation of candidate therapeutic antibodies using our unique animal model of human GBM recurrence.
The interns in this proposed cluster will be involved in 1) tracking GBM cell populations to determine the intracellular pathways that drive relapse and 2) the development of novel biologics to target specific proteins in these pathways under the direction of Prof. Moffat (UofT) as well as 3) testing these in animal models in Prof. Singh’s lab (McMaster).
A promising lead panel of biotherapeutics will be translated into early clinical development at the partner organization, CCAB, and its network of clinicians and industry partners with the hope of generating targeted therapies.