- Efficient cytosolic delivery and improved encapsulating / endosomal escape efficiency of Cyclic-di-GMP(c-di-GMP) by the structural feature
- Drastically enhanced antitumor effect by combination with anti-PD-1mAb
Background and Technology
Stimulator of interferon genes (STING) pathway agonists are now being extensively developed as a new class of cancer therapeutics. STING is an adaptor protein that plays an important role in the activation of type I interferons in response to cytosolic nucleic acid ligands. Recent evidence indicates involvement of the STING pathway in the induction of antitumor immune response. c-di-GMP is a STING ligand and was derived from natural substances and as the chemical synthesizing process was completed we were able to acquire c-di-GMP on a gram scale. However, the delivery efficiency to transmembrane was low.
The inventor group has constructed an original series of LNPs, named YSK05, YSK12-C4, YSK13 which have two fatty acid chains and unsaturated carbon chains. These LNPs loaded c-di-GMP effectively improved transmembrane, activated NK cells and induced antitumor effects against malignant melanomas and represent a possibility as a new adjuvant system for use in cancer immunotherapy.
WO2015/178343 (EP;15796352.1; US;15/311644,JP;2016-521092) and new patent application(not published yet)
Hideyoshi Harashima,Yusuke Sato / Faculty of Pharmaceutical Sciences, Hokkaido University
We are looking for a partner to develop or use appropriate LNPs from our library for drug delivery. We can share more data with you under CDA and provide you with samples of our LNPs under MTA.