This project leverages synthetic biomaterials to engineer the immune system, enhancing its response to internal threats like cancer and external challenges such as viral pathogens and toxic substances. By integrating chemistry, biotechnology, and nanotechnology, we target multiple aspects of immune function, including innate immune activation, antigen presentation, and adaptive immunity. For innate immunity, we develop delivery systems for immune-stimulatory agents (e.g., Toll-like receptor and STING agonists) to specific immune cell subsets in lymphoid organs and design strategies to mark cancer cells for recognition and elimination by innate effectors, thereby triggering tumor-specific adaptive responses. In the realm of antigen presentation, we create platforms to deliver peptides, RNA, proteins, and small molecule haptens alongside stimulatory molecules to antigen-presenting cells, optimizing immune priming and response specificity. For adaptive immunity, our approaches enhance T cell efficacy against tumors by overcoming immune-suppressive barriers within the tumor microenvironment. This multidisciplinary effort aims to establish robust, targeted immune responses, offering innovative therapeutic avenues for cancer and infectious diseases.