Unleashing the Power of STING Agonists: Driving Tumor-Specific Immune Responses

The abstract presents the pre-clinical evaluation of BI-STING, a compound that stimulates the STING signaling pathway, leading to a type 1 interferon response and pro-inflammatory cytokine secretion, which can trigger an anti-tumor immune response. The compound was tested in vitro, ex vivo, and in vivo to assess its activity and specificity in human cell lines and mouse models.

In vitro tests using the THP1 cell line demonstrated that BI-STING activates downstream signaling events specifically in cells with wild type STING, but not in STING knock out cells. Ex vivo studies in human whole blood and colorectal cancer slices showed significant cytokine secretion and transcriptional changes associated with STING activation upon BI-STING treatment.

In vivo studies involved intratumoral administration of BI-STING in various murine tumor models. This treatment led to a transient increase in cytokine levels in tumors and plasma, dose-dependent local tumor control, and the induction of a systemic anti-tumor immune response. Mice cured of their primary tumor by BI-STING did not develop new tumors upon re-challenge, and there was an abscopal effect on non-injected lesions. The abscopal tumor control was enhanced when BI-STING was combined with anti-PD-1 treatment. ELISpot analysis confirmed the induction of a tumor-specific immune response in treated animals.

The study concludes that BI-STING is a potent and specific inducer of the STING signaling pathway, capable of local tumor control and inducing a systemic anti-tumor immune response in mice. The efficacy of BI-STING as a monotherapy and in combination with anti-PD-1 is currently being evaluated in a clinical trial for patients with advanced solid tumors.