Grant: Project Grant

Cancer vaccines are treatments designed to train the immune system to recognize and destroy cancer cells. The most effective cancer vaccines need to generate strong "killer" T cell responses that can find and eliminate tumour cells throughout the body. Unfortunately, most current cancer vaccine candidates do not trigger enough of these T cells to be effective. One major reason is that the vaccine antigens - the molecular "targets" that T cells learn to recognize - are not taken up and processed efficiently by the immune system's key sentinels, known as antigen-presenting cells (APCs). In nature, a powerful way to deliver antigens to APCs is through immune complexes - clusters formed when antibodies bind to antigens. Immune complexes are known to enhance antigen capture, transport to immune hubs called lymph nodes, and activation of APCs. This process occurs naturally in booster vaccines against infectious diseases, but it has rarely been applied to cancer vaccines. Our research will uncover how the structure (such as size, shape, and arrangement of antigens) and composition (such as built-in immune stimulators) of immune complexes influence the quality of the immune response. To do this, we will use a nanotechnology tool called DNA origami, which acts as a molecular "breadboard" for arranging antigens and antibodies with nanometre precision. This will allow us to design immune complexes with controlled features, test how these designs affect APC activation, and determine which ones produce the most effective anti-cancer T cell responses in animal models. By revealing the "design rules" for building potent immune complexes, this work could guide the creation of more effective cancer vaccines. In the long term, these insights could also be applied to vaccines for infectious diseases, and to treatments for autoimmune disorders and transplant rejection.