Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity

Mol Ther. 2023 Jul 5;31(7):1938-1959. doi: 10.1016/j.ymthe.2023.03.026. Epub 2023 Mar 31.

Abstract

cGAS-STING signaling is a central component in the therapeutic action of most existing cancer therapies. The accumulated knowledge of tumor immunoregulatory network in recent years has spurred the development of cGAS-STING agonists for tumor treatment as an effective immunotherapeutic strategy. However, the clinical translation of these agonists is thus far unsatisfactory because of the low immunostimulatory efficacy and unrestricted side effects under clinically relevant conditions. Interestingly, the rational integration of biomaterial technology offers a promising approach to overcome these limitations for more effective and safer cGAS-STING-mediated tumor therapy. Herein, we first outline the cGAS-STING signaling axis and generally discuss its association with tumors. We then symmetrically summarize the recent progress in those biomaterial-based cGAS-STING agonism strategies to generate robust antitumor immunity, categorized by the chemical nature of those cGAS-STING stimulants and carrier substrates. Finally, a perspective is provided to discuss the existing challenges and potential opportunities in cGAS-STING modulation for tumor therapy.

Keywords: STING agonists; anti-tumor immunity; cGAS-STING pathway; cancer therapy; nanointegrated drug delivery.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / immunology
  • Biocompatible Materials*
  • Excipients*
  • Immunity, Innate
  • Immunization
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Nucleotidyltransferases / genetics
  • Signal Transduction

Substances

  • Biocompatible Materials
  • Excipients
  • Nucleotidyltransferases
  • cGAS protein, human
  • STING1 protein, human
  • Antineoplastic Agents