Enhancing the antitumour potency of a STING agonist via conjugation to a systemically delivered polymeric nanoparticle

Description:
The effectiveness of intravenously administered cyclic dinucleotides (CDNs) and other stimulator of interferon genes (STING) agonists is hampered by low cellular uptake and poor circulatory half-life. While electrostatic binding of nucleic acids to nanoparticles (NPs) can be effective, this is not the case for small molecules such as CDNs. Covalently conjugating CDN to poly(beta-amino ester) nanoparticles (CDN-NPs) through a cathepsin-sensitive linker, as opposed to electrostatic formulations, increased NP stability and CDN loading, thereby expanding the therapeutic window in multiple syngeneic tumor models. We investigated the effect of the long-term fate of the nanoparticles on the immune response. In a melanoma mouse model, primary tumor clearance depended on STING signaling by host cells, rather than cancer cells, and immune memory depended on the spleen; yet cancer cells acted as a depot for CDN-NPs, releasing them over time to activate nearby immune cells to control tumor growth. Collectively, this work highlights the importance of NP structure and nano-bio interactions in controlling immunotherapy efficacy.

Speaker: Natalie Artzi - Harvard Medical School and MIT
Dr. Artzi is an Assistant Professor of Medicine at Harvard medical School. She is a Principal Research Scientist at MIT, Associate Faculty at the Wyss Institute for Biologically Inspired Engineering, and an Associate Member of the Broad Institute of Harvard and MIT. She completed her postdoctoral studies at MIT focusing on studying tissue:biomaterial interactions and designing smart biomaterials for therapy and diagnosis applications.

Dr. Artzi is the recipient of multiple grants and awards, including the inaugural Kabiller Rising Star Award in Nanotechnology and Nanomedicine, the One Brave Idea award, Stepping Strong Innovator Award, Controlled Release Society Young Investigator Award, Mid-Career Award from the Society for Biomaterials, Bright Futures Prize, and the Massachusetts Life Science Center for women entrepreneurs.

Dr. Artzi directs multiple research venues integrating science, engineering and medicine to rationally design materials to improve human health.