Nanomedicine stands to make major contributions to immunotherapy. Nanostructures that can be designed to present and deliver immunestimulatory molecules to cells of the immune system provide a way to boost, modulate and tune immune responses to disease. Spherical nucleic acids (SNAs) are a specific and promising class of nanostructure that are we are developing as immunotherapeutic vaccines for cancer. In spite of what is known about the molecular pathways for immune system stimulation and antigens specific for many types of cancer, cancer vaccines have historically not shown outstanding success clinically. What remains poorly understood is how best to deliver and present antigen and adjuvant molecules to the immune system. SNAs have the characteristic feature of a nanoparticle core presenting chemically functionalized TLR agonist oligonucleotides at high surface density. SNAs are structurally well-defined and modular in nature; through synthetic chemistry, we have controlled several structural features of SNAs independently (e.g., core composition and size, position of antigen). This approach has enabled our rational design of vaccines based on SNA structures and has identified several structural features critical for stimulating anti-cancer immune responses. We have found that variations in the structures of SNAs, those that are compositionally equivalent but structurally distinct, lead to major differences in the quality of induced antigen-specific immune responses. Our development of SNAs as potential cancer vaccines has not only led to the identification of structures that generate anti-tumor responses and survival benefits in vivo, but has also allowed us to establish the structural and mechanistic basis for function and to drive further improvements in vaccine design.

This short presentation dives into a portion of the book, "Prometheans in the Lab." Most people today know that lead poses some health risk. But the book transports us to a time where lead was everywhere, even in our toothpaste containers. I would like to talk about the driving factors in science when health was no issue. What did leaded fuel succeed at doing? What did it fail at?

Andrew Lee is a Research Assistant Professor at Northwestern University, in the Department of Chemical and Biological Engineering. Following his PhD training in chemistry at Harvard University post-doctoral training at Northwestern University, he began an appointment as an independent investigator at Northwestern University. Andrew Lee’s activity in nanomedicine research involves the development of spherical nucleic acid (SNA) nanostructures as therapeutic agents for the treatment of cancer (immunotherapeutic or gene regulatory mechanisms of action), in research programs led by Professor Chad Mirkin at Northwestern University. This research is examining the chemical composition and structure of SNAs (the core, oligonucleotide, and antigen and peptide-conjugation chemistries) as the drivers of the ability of SNAs to function as agents that enter targeted cells and enhance the activity of therapeutic oligonucleotides (as immunostimulatory compounds). These research efforts are supported by the National Cancer Institute and Prostate Cancer Foundation. Related research projects, aimed at innovating vaccine immunotherapy for prostate cancer, are focused on discovering neoantigens through the identification of post-translationally modified proteins and analysis of the immunogenicity of these proteins.