中国化学会第32届学术年会
重要日期
注册参加会议 登录会议管理
线上墙报
(R)Phosphorothiated c-di-GMP Encapsulated by DNCA/CLD as STING Agonist Shows much Stronger Anti-tumor Immunity
于小桐 代宏 杨振军*

分会

第三十二分会:化学生物学

摘要

Cyclic dinucleotides (cDNs) have been emerging as a promising class of immunotherapeutics targeting STING (Stimulator of Interferon Gene). However, the enzymatic instability and transmembrane barriers hinder cDNs from extensive clinical applications. In this study, we encapsulate cDNs with a neutral cytidinyl lipid DNCA and a cationic lipid CLD(Mix) via H-bonding, pi-stacking and electrostatic interaction. The optimal formulation, c-di-GMP(cdG)/Mix (500 nM), could induce 50-fold IFN-Ⅰ release compared with soluble cdG. In addition, its RP stereoisomer of monothiophosphate analogue showed much more potency for IFN-Ⅰ induction, while SP stereoisomer could hardly elicit the induction of IFN-Ⅰ. It has been confirmed that cDNs/Mix resulted in stronger anti-tumor efficacy and tumor growth inhibition in two murine tumor models. The mice with melanoma administered 5 μg cdG/Mix intratumorally showed 42.9% long-term survival, and 83% rechallenge mice obtained resistance to specific tumor and established memory immunity. Besides, 1 μg cdG/Mix i.t. administration could significantly inhibit tumor growth in breast cancer murine model, showing almost equal anti-tumor efficacy relative to 10 μg group. Importantly, cdG/Mix intravenously administration could also significantly inhibit tumor growth and result in a 11% long-term survival, which offering a treatment opportunity to patients with non-accessible cancer.

关键词

Cyclic dinucleotides; DNCA; CLD; Tumor immunotherapy; STING nanoparticle

线上墙报仅限年会已缴费参会代表观看。

您还没有登录,请您先 点击这里登录