刺
癌症免疫疗法
免疫疗法
免疫系统
癌症研究
医学
干扰素基因刺激剂
抗体
癌症
免疫学
先天免疫系统
药理学
内科学
工程类
航空航天工程
作者
Youtong Wu,Yan Fang,Wei Qi,Heping Shi,Huiling Tan,Yafang Deng,Zhiqun Zeng,Jian Qiu,Chuo Chen,Lijun Sun,Zhijian J. Chen
标识
DOI:10.1073/pnas.2214278119
摘要
The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells. Systemic administration of these ADCs was well tolerated and exhibited potent antitumor efficacy in syngeneic mouse tumor models. The STING ADC further synergized with an anti-PD-L1 antibody to achieve superior antitumor efficacy. The STING ADC promoted multiple aspects of innate and adaptive antitumor immune responses, including activation of dendritic cells, T cells, natural killer cells and natural killer T cells, as well as promotion of M2 to M1 polarization of tumor-associated macrophages. These results provided the proof of concept for clinical development of the STING ADCs.
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