Novel formulation of c-di-GMP with cytidinyl/cationic lipid reverses T cell exhaustion and activates stronger anti-tumor immunity.

ABSTRACT: Rationale: Cyclic dinucleotides (cDNs) are a promising class of immunotherapeutic agent targeting stimulator of interferon genes (STING). However, enzymatic instability and transmembrane barriers limit the extensive clinical application of cDNs. Thus, a novel delivery system, composed of a neutral cytidinyl lipid DNCA and a cationic lipid CLD (Mix) that interacts with cDNs via H-bonding, pi-stacking and electrostatic interaction, is developed and optimized to overcome the above issues. Methods: The optimal composition of Mix for cDNs encapsulation was explored with RAW-Lucia ISG cells. The physicochemical properties of resulted nanoparticles were characterized. To validate the anti-tumor immunity of cDNs/Mix both in vitro and in vivo, immunogenic cell death (ICD

SUBMITTER: Yu X 

PROVIDER: S-EPMC9516232 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature