A novel biopolymer synergizes type I IFN and IL-1β production through STING

Abstract

N-dihydrogalactochitosan (GC) is developed for inducing immune responses. Synthesized from chitosan and galactose, GC is a new chemical entity that significantly enhances the immune-stimulating properties of its parental material, chitosan, making it a promising therapeutic agent. When used in combination with antigenic material, GC stimulates innate and adaptive antitumor and antiviral immunities. However, the mechanism of GC has not been fully investigated. Herein we demonstrate that GC drives type I IFN production and IFN responses in antigen presenting cells (APCs) and has superior potency compared to its corresponding chitosan. More importantly, GC drives alternative activation of STING leading to inflammatory cell death that enhances dendritic cell (DC) activation, which triggers a variety of nucleic acid sensing pattern recognition receptors (PRRs) and IL-1b production. In vivo, GC induced a potent response of type I IFN and upregulated genes associated with STING signaling within the tumor microenvironment (TME). Moreover, intratumoral delivery of GC reduced the numbers of M2-like macrophages residing within the TME, while subsequently increasing the number of DCs. Our findings demonstrate GC's unique ability to activate STING and stimulate a broad type I IFN response which holds therapeutic promise in generating antitumor and antiviral immunities.

A novel biopolymer for mucosal adjuvant against respiratory pathogens

“…Because of its physical and chemical properties, GC poses strong retention power in retaining antigens at the administration site at an appropriate concentration, as shown in Figure 1A and Supplemental Figure 1B. Furthermore, GC activated several different nucleic acid PRRs (Figure 1C), all of which were downstream of STING signaling and led to type I IFN and IL-1β production 26 . GC also activated immune pathways involved in response to Covid-19, as shown in Figure 1B.…”

“…Furthermore, GC activated several different nucleic acid PRRs (Figure 1C), all of which were downstream of STING signaling and led to type I IFN and IL-1β production 26 . GC also activated immune pathways involved in response to Covid-19, as shown in Figure 1B.…”

“…To overcome these and other limitations of existing mucosal adjuvants, we developed Ndihydrogalactochitosan (GC), a new molecule that is synthesized from galactose and chitosan 23 . Compared to the immune responses induced by its chitosan precursor 24,25 , GC exhibits superior potency in inducing the type I IFN pathway 26 . In addition, GC has improved solubility over chitosan, and retains many of the favorable properties of chitosan, including its low toxicity, biodegradability, low-pH resistance, biocompatibility, and mucoadhesive nature.…”