STING Ligands Rationally Design

STING has emerged as a promising target for the development of novel immunization, autoinflammation, and cancer therapeutics. Especially, the development of STING agonist which can recruit T-cells at the site of tumors is expected to greatly improve the efficacy of vaccines. Creative Biolabs is a world leader in the field of vaccine development who has focused on the cancer vaccines for years. The extensive experience and expertise of our scientists enable Creative Biolabs to provide innate immune stimulators related development services, including STING ligands rationally design.

Stimulator of Interferon Gene (STING)

Stimulator of interferon gene (STING) plays an important role in the innate immune system and it is the first line of defense against pathogenic invasion of bacteria and viruses. Indeed, the adjuvant activity of DNA-based vaccines has been shown to be mediated by STING stimulation, which can elicit antigen-specific CTL responses. In addition to being an effective vaccine adjuvant, several STING ligands have been shown to exert anti-tumor effects. For example, the synthetic STING ligand 5,6-dimethylxanone-4-acetic acid (DMXAA) achieves a potent anti-tumor immune response in mice. Other STING ligands, including cyclic dinucleotides such as cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), cyclic diguanylate and cyclic deadenylate, are capable of enhancing anti-tumor immune responses when used as vaccine adjuvants or immunotherapeutic agents.

STING activation pathways.

Fig.1 STING activation pathways. (Li Y. 2017)

STING Ligands

As a potent type I interferon (IFN) inducer, 5,6-Dimethylxtonone-4-acetic acid (DMXAA) can be used as cancer vaccine adjuvant. Clinical trials have shown that DMXAA is safe and well tolerated in humans.

cGAMP, which can enhance the efficacy of vaccine-induced CD8+ T cells, is currently being developed as adjuvants in various formulations to optimize the efficacy and immunogenicity of vaccines.

Cyclic dinucleotides are unique nucleic acids functioning as conserved signaling molecules in bacteria and can induce a STING-dependent type I IFN response, which have shown promise as novel vaccine adjuvants.

Bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) is a second messenger molecule in bacteria and archaea which can exert strong adjuvant activity when delivered by mucosal route.

When administered by mucosal or systemic routes, c-di-IMP exhibits potent activity as an adjuvant. It has comparable capacities to c-di-GMP in promoting the activation and maturation of DC and enhancing stimulatory capacities on macrophages.

As a central protein in the innate immune response of intracellular DNA, STING has emerged as a hot target for vaccine adjuvants and anticancer drug development. The discovery of potent human STING agonists is expected to revolutionize current cancer immunotherapy. Creative Biolabs is specialized in assisting clients with every stage of the vaccine industry, including STING agonists development. As an innovative and truly premier drug discovery and development research partner, Creative Biolabs is committed to providing the best quality services and high level of specialized support.

Reference

  1. Li Y, et al. Regulating STING in health and disease. J Inflamm (Lond). 2017, 14: 11.

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