5,6-dimethylxanthenone-4-acetic acid (DMXAA) as Vaccine Adjuvant

As a potent type I interferon (IFN) inducer, 5,6-dimethylxanthenone-4-acetic acid (DMXAA) can be used as cancer vaccine adjuvant. Clinical trials have shown that DMXAA is safe and well tolerated in humans. Creative Biolabs is a leader in the field of vaccine development and the extensive experience and expertise of our scientists enable us to provide development services related to innate immune stimulators, particularly the adjuvant development of DMXAA.

5,6-dimethylxanthenone-4-acetic Acid (DMXAA)

5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a potent type I IFN inducer, which has a variety of biological functions and acts as an activator of soluble innate immunity. The xanthenone derivative compound DMXAA was originally identified as a small molecule that exhibits immune modulatory activities by inducing cytokines and disrupts tumor vascularization in various mouse models. DMXAA has the ability to improve antigen-specific immune responses and induce preferential Th2 (type 2) responses and demonstrates good tolerance in human cancer clinical trials. The adjuvant effect is directly dependent on IRF3-mediated type I interferon production but is not dependent on IL-33.

Fig.1 Patel’s X-ray crystal structures of DMXAA bound to mutated hSTING. (A) The 2.37 Å crystal structure of DMXAA bound to hSTING^{S162A/G230I/Q266I}. (B) Crystal structure representation of DMXAA bound to hSTING^{S162A/G230I/Q266I} with an emphasis on hydrophobic interactions around DMXAA. (C) The 2.51 Å crystal structure of DMXAA bound to hSTIN^GG230I with representation of hydrogen bonding as dotted line, color coded. (Hwang J. 2019)

DMXAA as Cancer Vaccine Adjuvant

As a cell-permeable small molecule, DMXAA reduces tumor load by inducing apoptosis of tumor vascular endothelial cells, thus reducing blood flow to solid tumors. Further research has shown it to be a potent immunogenic molecule and has therefore been developed as a vascular disrupting agent for cancer therapy. Some clinical trials have shown that DMXAA is safe and well tolerated in humans.

The anti-tumor properties of DMXAA are mainly due to its induction of TNFα, which activates several inflammatory cell signaling pathways, including c-Jun N-terminal kinases, extracellular signal-regulated kinases 1 and 2, and cytosolic nucleotide-binding oligomerization domain 1 and 2-like receptors.
DMXAA is a strong inducer of reactive oxygen species (ROS). The most striking immunogenic feature of DMXAA is its induction of immediate and major type I IFN. Similar to viral infections and double-stranded DNA (dsDNA) in inflammatory signaling events, DMXAA triggers induction of type I IFN production. It uses the TBK1-IRF3 signaling pathway and does not involve the Toll-like receptor (TLR) or RNA helicase for its type I IFN-induced mechanism.
Furthermore, DMXAA can also induce direct activation of antigen presenting cells (APCs) such as macrophages and dendritic cells (DCs).

Creative Biolabs is specialized in assisting clients with every stage of the vaccine development services, including adjuvant optimization. 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

Hwang J, et al. Design, synthesis, and biological evaluation of C7-functionalized DMXAA derivatives as potential human-STING agonists. Org Biomol Chem. 2019, 17(7): 1869-1874.

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.