Grant: Operating Grant: Industry-partnered Collaborative Research

Our goal is to search for new anti-cancer drugs by screening a natural product library made from deep-sea sponges. We will be specifically looking for compounds that make the cancer cell recognizable to the host immune system, since many cancer cells are able to hide from host immune cells. Many metastatic tumours are able to hide from the immune system. We have previously established that this is often due to down-regulation of the antigen presentation pathway (APP) components within the cancer cell. The normal function of the APP is to allow a molecule known as the Major Histocompatibility Complex class I (or MHC-I) to get to the cell surface. This MHC-I acts as a flag for the immune system, to let it know whether the cell is healthy or cancerous. Using a cancerous cell line that has previously been shown to express low numbers of MHC-I, we have developed a high-throughput screening to identify extracts and compounds that would boost the expression of the cellular MHC-I and take away the ability of the cancer cell to hide from the immune system. The promising marine extracts will be selected for further work, including testing the toxicity of the extracts, and isolation and identification of the active compounds within the extract. We have now identified new and unique chemical entities that provide new intellectual property. Our ultimate goal is to identify new anti-cancer compounds that can be tested to see if they stop cancer in animal models and eventually in human clinical trials. We have obtained preliminary evidence that a number of these compounds are uniquely able to improve immune recognition on metastatic tumours and therefore, may have utility to harness the power of the immune response as a therapy for cancer. Ultimately, these new compounds may be promising anti-cancer agents.