Rational Vaccinology: Harnessing Nanoscale Chemical Design for Cancer Immunotherapy

[Image: see text] Cancer immunotherapy is a powerful treatment strategy that mobilizes the immune system to fight disease. Cancer vaccination is one form of cancer immunotherapy, where spatiotemporal control of the delivery of tumor-specific antigens, adjuvants, and/or cytokines has been key to successfully activating the immune system. Nanoscale materials that take advantage of chemistry to control the nanoscale structural arrangement, composition, and release of immunostimulatory components have shown significant promise in this regard. In this Outlook, we examine how the nanoscale structure, chemistry, and composition of immunostimulatory compounds can be modulated to maximize immune response and mitigate off-target effects, focusing on spherical nucleic acids as a model system. Furthermore, we emphasize how chemistry and materials science are driving the rational design and development of next-generation cancer vaccines. Finally, we identify gaps in the field that should be addressed moving forward and outline future directions to galvanize researchers from multiple disciplines to help realize the full potential of this form of cancer immunotherapy through chemistry and rational vaccinology.