Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 49, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2214278119
Keywords
cGAS; STING; ADC; cancer; tumor immunity
Categories
Funding
- ImmuneSensor Therapeutics
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available