Identifying and validating rational combinatorial therapies for treatment-refractory Glioblastoma

Glioblastoma (GBM), the most common and deadly form of primary brain cancer in adults. After diagnosis, GBM patients undergo standard therapy, including surgery, chemotherapy and radiation therapy. Unfortunately, disease relapse is inevitable and patients face a median survival of less than 15 months. A small population of tumor cells, known as brain tumor initiating cells (BTICs), have been shown to resist standard therapy and lead to relapse. Using a multi-pronged approach, we are developing novel and rational combinatorial therapies against treatment-resistant GBM BTICs.

Investigating the scope of dsRNAi in human cells

Long dsRNA is produced by viruses during their replicative cycle. In plants and invertebrates, long dsRNAs block crucial cellular processes through RNA interference (RNAi). In vertebrates, long dsRNA is a potent inducer of critical signaling proteins that regulate antiviral immune responses. Although the RNAi system is conserved in vertebrates, there is little evidence to suggest that it plays a major role in antiviral defense. Moreover, it remains unclear whether long dsRNA can function as a template for RNAi (dsRNAi) in vertebrates.

Systematic evaluation and optimization of immune-targeting modalities for GBM and brain metastases.

The Centre for the Commercialization of Antibodies and Biologics (CCAB) is working with Empirica Therapeutics (Empirica), a Canadian start-up company focused on developing data-driven treatments for cancer, to address the unmet medical needs of glioblastoma (GBM), the most common adult malignant primary brain tumor. Current therapies are only partly effective, with frequent relapse and poor patient survival, which correlates with the presence of CD133+ brain tumor-initiating cells that are also implicated in treatment-resistant GBM. By partnering with Dr.

CRISPR-Cas9-based screening and engineering of novel biologics to target the vulnerabilities of primary and recurrent glioblastoma

Glioblastoma (GBM) is the most common primary adult brain tumor. Even with surgery, standard chemotherapy, and radiation, tumor recurrence and patient relapse are inevitable with a median survival rate of

Development and Delivery of Inhibitors for Viral Pathogenic Deubiquitinases - Year Two

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.

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

Development of Cell-Based Functional Assays to Accelerate Commercialization and Therapeutic Application of Recombinant Antibodies

Antibodies are used for treatment of many diseases, including cancer. Within the human immune system, antibodies fight invading bacteria and viruses. We have devised a way to make high-quality antibodies in the laboratory and target them to specific disease-related proteins that have been identified by the scientific community and in our lab. Ensuring that these antibodies work in cells the way we intend them to in the body is a critical step of identifying their potential as therapeutic agents and also in the commercialization process.

Development of dual antibody therapies for cancer

Cancer is a devastating disease defined by genetic changes that result in the activation of proteins that encourage cell growth or prevent cell death. Modern oncology aims to specifically target these tumour-promoting proteins, which has the secondary benefit of leaving normal cells unharmed, unlike chemotherapy. Recently, a number of drugs that specifically block tumour-promoting proteins have been produced, yet the results are underwhelming: most targeted therapies show an initial benefit, followed by the development of resistance.

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.

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.