Immune checkpoint inhibition (ICI) immunotherapy has transformed cancer treatment for a number of malignant diseases. However, not all patients with cancer benefit from ICI. Only a minority of patients respond with long lasting benefit, patients can experience significant toxicity and resistance to therapy can emerge. Tumor neoantigens arise from mutations in a tumor’s DNA and can serve as targets of the immune system. ICI relies on augmenting existing anti-tumor immunity in patients. Therefore, one approach to increase ICI efficacy is to boost anti-tumor immunity by neoantigen vaccination. This has encouraged the pursuit of a personalized cancer vaccine which specifically targets a patient’s tumor neoantigens and enhances ICI. However, so far, attempts to generate personalized neoantigen vaccines for cancer have shown limited success. Two major obstacles remain for the development of a personalized cancer vaccine: 1) The efficient identification of neopeptides that stimulate T cell immunity and 2) the lack of a highly immunogenic vaccine strategy to target neopeptides.
We hypothesize that a highly immunostimulatory neopeptide cancer vaccine will improve ICI therapy. The overarching aim of the proposal is to use novel neoantigen prediction pipelines and vaccine strategies to develop an efficient personalized cancer vaccine that improves ICI therapy.
Our proposal will develop a personalized neoantigen-based vaccine that improves the efficacy of checkpoint inhibition therapy in cancer. The vaccine would also improve quality of life for patients by reducing tumor burden. Our proposal clearly meets 2/3 of the KWF’s mission goals of less cancer, more cure and a better quality of life.