Development of small-molecule sting activators for cancer immunotherapy

Hee Ra Jung, Seongman Jo, Min Jae Jeon, Hyelim Lee, Yeonjeong Chu, Jeehee Lee, Eunha Kim, Gyu Yong Song, Cheulhee Jung, Hyejin Kim, Sanghee Lee

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

In cancer immunotherapy, the cyclic GMP–AMP synthase–stimulator of interferon genes (STING) pathway is an attractive target for switching the tumor immunophenotype from ‘cold’ to ‘hot’ through the activation of the type I interferon response. To develop a new chemical entity for STING activator to improve cyclic GMP-AMP (cGAMP)-induced innate immune response, we identified KAS-08 via the structural modification of DW2282, which was previously reported as an anti-cancer agent with an unknown mechanism. Further investigation revealed that direct STING binding or the enhanced phosphorylation of STING and downstream effectors were responsible for DW2282-or KAS-08-mediated STING activity. Furthermore, KAS-08 was validated as an effective STING pathway activator in vitro and in vivo. The synergistic effect of cGAMP-mediated immunity and efficient anti-cancer effects successfully demonstrated the therapeutic potential of KAS-08 for combination therapy in cancer treatment.

Original languageEnglish
Article number33
JournalBiomedicines
Volume10
Issue number1
DOIs
Publication statusPublished - 2022 Jan

Keywords

  • Cancer immunotherapy
  • STING
  • STING activator
  • Type I interferon

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'Development of small-molecule sting activators for cancer immunotherapy'. Together they form a unique fingerprint.

Cite this