Tumor-targeted delivery of a STING agonist improves cancer immunotherapy

You Tong Wu, Yan Fang, Qi Wei, Heping Shi, Huiling Tan, Yafang Deng, Zhiqun Zeng, Jian Qiu, Chuo Chen, Lijun Sun, Zhijian J. Chen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Article numbere2214278119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number49
StatePublished - Dec 6 2022
Externally publishedYes


  • ADC
  • cancer
  • cGAS
  • tumor immunity

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Tumor-targeted delivery of a STING agonist improves cancer immunotherapy'. Together they form a unique fingerprint.

Cite this