The clinical success of cancer immunotherapies has reinvigorated the discovery for novel immune stimulants. Selective activation of the innate immune system to generate an adaptive immune response has long been a goal for drug discovery. Systemically delivered small molecule Toll-like receptor (TLR) agonists have been vigorously pursued in the clinic but have suffered from undesirable side-effects, mainly attributed to the inherent mode of action. To overcome these liabilities, we developed an immune-stimulating antibody conjugate (ISAC) platform. ISACs are tumor-targeting monoclonal antibodies that systemically deliver a powerful innate immune-stimulating agent directly to the tumor microenvironment. Pre-clinical data will be presented demonstrating an adaptive immune response leading to durable T cell mediated tumor clearance and surveillance through TLR7/8 agonism. The structure-based design of novel TLR7/8 agonists will be presented. Optimization of TLR7/8 potency, selectivity and linker chemistry will be described in the context of ISAC potency and in vivo efficacy. Bolt’s approach to this new class of immuno-oncology therapeutics demonstrates the promise of the ISAC platform.

Discovery of tumor-targeted TLR7/8 immune-stimulating antibody conjugates (ISACs): New class of immuno-oncology therapeutics

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.