Scientists pinpoint new vaccine adjuvant that promotes potent anti-tumor immunity

Good news! Cancer is history (soon)!

"Scientists ... have made an important breakthrough that offers promise for developing new immune therapies for cancer. They have discovered that a vaccine adjuvant called C100 promotes potent anti-tumor immunity when it is injected directly into tumors in an animal model. ...

The scientists found that C100, derived from chitin—one of the most common building materials in nature, and which gives strength to the exoskeletons of crustaceans, insects, and the cell walls of fungi—is highly effective at stimulating a key sensing and signaling molecule which regulates anti-tumor immune responses. ..."

From the highlights and abstract:

"Highlights

• Intratumoral injection of the adjuvant C100 promotes potent anti-tumor immunity

• Adjuvant functionality requires STING and IFNAR signaling and CD8+ T cells

• C100 injection synergizes with systemic checkpoint blockade with anti-PD1

• C100 triggers DNA damage to selectively activate the IFN arm of the cGAS-STING pathway

Summary

Stimulator of IFN genes (STING) is a promising target for adjuvants utilized in in situ cancer vaccination approaches. However, key barriers remain for clinical translation, including low cellular uptake and accessibility, STING variability necessitating personalized STING agonists, and interferon (IFN)-independent signals that can promote tumor growth. Here, we identify C100, a highly deacetylated chitin-derived polymer (HDCP), as an attractive alternative to conventional STING agonists. C100 promotes potent anti-tumor immune responses, outperforming less deacetylated HDCPs, with therapeutic efficacy dependent on STING and IFN alpha/beta receptor (IFNAR) signaling and CD8+ T cell mediators. Additionally, C100 injection synergizes with systemic checkpoint blockade targeting PD-1. Mechanistically, C100 triggers mitochondrial stress and DNA damage to exclusively activate the IFN arm of the cGAS-STING signaling pathway and elicit sustained IFNAR signaling. Altogether, these results reveal an effective STING- and IFNAR-dependent adjuvant for in situ cancer vaccines with a defined mechanism and distinct properties that overcome common limitations of existing STING therapeutics."

Scientists pinpoint new vaccine adjuvant that promotes potent anti-tumor immunity

Intratumoral delivery of the chitin-derived C100 adjuvant promotes robust STING, IFNAR, and CD8+ T cell-dependent anti-tumor immunity (open access)

Graphical abstract