John Wilson, Blaise Kimmel, Karan Arora, Neil Chada, Vijaya Bharti, Alexander Kwiatkowski, Jonah Finklestein, Ann Hanna, Emily Arner, Taylor Sheehy, Lucinda Pastora, Jinming Yang, Hayden Pagendarm, Payton Stone, Brandie Taylor, Lauren Hubert, Kathern Gibson-Corley, Jody May, John McLean, Jeffrey Rathmell, Ann Richmond, Wendy Rathmell, Justin Balko, Barbara Fingleton, Ebony Hargrove-Wiley
Stimulator of interferon genes (STING) is a promising target for potentiating antitumor immunity, but multiple pharmacological barriers limit the clinical utility, efficacy, and/or safety of STING agonists. Here we describe a modular platform for systemic administration of STING agonists based on nanobodies engineered for in situ hitchhiking of agonist cargo on serum albumin. Using site-selective bioconjugation chemistries to produce molecularly defined products, we found that covalent conjugation of a STING agonist to anti-albumin nanobodies improved pharmacokinetics and increased cargo accumulation in tumor tissue, stimulating innate immune programs that increased the infiltration of activated natural killer cells and T cells, which potently inhibited tumor growth in multiple mouse tumor models...
May 8, 2024: Research Square