期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2214278119
关键词
cGAS; STING; ADC; cancer; tumor immunity
资金
- ImmuneSensor Therapeutics
The study demonstrates the development of antibody-drug conjugates (ADCs) by conjugating a STING agonist to tumor-targeting antibodies, which showed well-tolerated systemic administration and potent antitumor efficacy. The STING ADC also promoted multiple aspects of antitumor immune responses, highlighting its potential for clinical development.
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 intra-tumoral 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据