Grant: Vaccines of the 21st Century

In Canada, colorectal cancer is the fourth most prevalent cancer and the second leading cause of cancer death. New approaches to colorectal cancer control are needed. Over 100 years of research have shown that the immune system can and does prevent cancer by recognizing and killing cells that have cancer causing mutations. Nearly all malignant colorectal cancers arise from earlier benign growths called intestinal polyps and this progression is typically initiated by specific mutations in genes that regulate cell division. In principle, if the immune system of people at risk for developing colorectal cancer could be primed by vaccination to recognize these mutations as they occur, then in many instances the progression from benign polyps to malignant colorectal cancers could likely be prevented. However, immunity is usually conferred by very small and specific pieces of mutated gene products. The exact pieces are hard to predict, and there can be considerable variation among individuals in how effective the pieces are in generating immunity. It remains unknown which pieces of the mutated gene products in colorectal cancer would be useful to use in a vaccine. In the present study we will take a comprehensive approach to evaluating individuals with either benign polyps or colorectal cancers to determine which pieces of the commonly mutated proteins have actually stimulated an immune response, and how the response varies from one person to another. Our findings from this pilot study will be essential for the design of a larger validation study, and will generate important information to guide ongoing efforts to develop a progression blocking vaccine for colorectal cancer.