Therapeutics that can harness the immense power and specificity of the immune system have enormous potential to improve human health. Cells of the immune system sense invading pathogens and/or pathology using a network of receptors that act cooperatively to enhance and shape the type and magnitude of an immune response. Hence, regulating the delivery of immunologic cues to the tissues, cells, and pathways of the immune system is fundamental to guiding immunological decision-making. While most therapeutic strategies to modulate immunity target cell surface or endo/lysosomal receptors, the cytosol is also rich in targets for immunomodulation. However, the development of therapeutics that harness these immune surveillance pathways is hindered by major drug delivery barriers, most notably inefficient delivery to cytosolic targets. This talk will focus on research in my laboratory focused on the molecular engineering of nanostructured, supramolecular polymeric materials that enhance intracellular delivery of immunomodulatory proteins, nucleic acids, and small molecules. I will discuss our efforts in developing pH-responsive, endosome-destabilizing “smart” materials for enhanced cytosolic delivery of antigens and immunostimulatory nucleic acids and the application of these approaches in cancer immunotherapy and vaccines for infectious disease. In particular, I will discuss our recent work in the following areas. First, I will describe the development and preclinical evaluation of polymersomes for efficient cytosolic delivery of cyclic dinucleotide STING agonists and describe how we are leveraging this technology to enhance responses to immunotherapy in multiple ways in a diversity of cancer types. Second, I will discuss the development of nanoparticle-based vaccines for installing tissue resident memory T cells at mucosal interfaces and the capacity of these materials to protect against respiratory infections. Collectively, these results highlight the potential to design and leverage self-assembled, pH-responsive materials to open access to cytosolic immune surveillance pathways with potential to lead to next generation immunotherapies and vaccines for a diversity of diseases.

Engineering smart nanotechnologies to harness cytosolic immune surveillance machinery

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.