Innate immune activation is an important hallmark in cancer immunotherapy and can be provoked by potent small molecule agonists of pathogen associated molecular patterns. However, uncontrolled triggering evokes systemic inflammatory immune responses and hampers clinical translation of several classes of small molecule immune modulators.<br/>Here we present a technology that delivers small molecule immune modulators to lymphoid tissue and abrogates systemic dissemination. Our strategy comprises an amphiphilic lipid-polymer carrier to which a small molecule immune modulators is conjugated. By hitch hiking the albumin flow in interstitial tissue, these conjugates are extremely efficiently transported to secondary lymphoid tissue upon local administration where they are taken up by innate immune cells and potently activate these. We provide a proof-of-concept using an imidazoquinoline-based agonist of Toll-like receptors 7 and 8 in both a cancer immunotherapy and vaccine adjuvant setting, showing enhanced efficacy and safety. Importantly, our strategy can be universally applied to any small molecule that has a chemical handle for conjugation and that has lymphoid tissue as target organ. <br/>

Spatial control over innate immune activation by imidazoquinoline TLR7/8 agonists through lipid polymer amphiple conjugation

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.