Conjugated STING agonists

Abstract

An innate immune system is the first line of defense and prevents the host from infection and attacks the invading pathogens. Stimulator of interferon genes (STING) plays a vital role in the innate immune system. STING activation by STING agonists leads to phosphorylation of TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) with the release of type I interferons and proinflammatory cytokines, further promoting the adaptive immune response and activating T cells by increased antigen presentation. Natural STING agonist cyclic dinucleotides (CDNs) encounter many defects such as high polarity by negative charges, low stability and circulative half-life, off-target systemic toxicity, and low response efficacy in clinical trials. To overcome these challenges, massive efforts have addressed chemical modifications of CDNs, development of non-CDN STING agonists, and delivery of these STING agonists either by conjugation or liposomes/nanoparticles. Considering there have been a great number of reports regarding nanosystem-aided delivery, here, we examine the development of STING agonists, especially for non-CDNs and their delivery specifically by conjugation strategy, with a focus on the STING agonists in clinical trials and current challenges of their potential in cancer immunotherapy.

Keywords

• MT: Delivery Strategies
• stimulator of interferon genes
• STING
• STING agonists
• conjugated
• CDNs