Xenetic Biosciences Shows DNase I Boosts Anti-CTLA-4 Efficacy in Colorectal Cancer Models

Xenetic Biosciences, Inc. (NASDAQ: XBIO), a biopharmaceutical company focused on developing innovative immuno-oncology technologies for challenging cancer treatments, recently announced promising preclinical data. The findings were shared at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) held from November 6-10, 2024, in Houston, Texas, and virtually. The presentation, titled "DNase I Targeting of Neutrophil Extracellular Traps Improves CTLA-4 Immune Checkpoint Blockade in Models of MSS/MMRp CRC," was given by Dr. Reid Bissonnette, Executive Consultant for Translational Research and Development at Xenetic.

Xenetic's platform focuses on DNase I, which targets Neutrophil Extracellular Traps (NETs). NETs are web-like structures that contribute to an immunosuppressive tumor microenvironment (TME) and are prevalent in several cancers, including colorectal cancer (CRC). The preclinical study used mouse models implanted with CT26 or Colon26 cells, representing microsatellite stable, mismatch repair proficient (MSS/MMRp) CRC. The study examined the combination of DNase I and anti-CTLA-4 antibodies, with treatments administered either daily or biweekly.

The results demonstrated that targeting NETs with DNase I significantly improved the efficacy of CTLA-4 immune checkpoint blockade. This combination therapy hindered neutrophil tumor infiltration and promoted the infiltration and activation of CD4 and CD8 T cells within the tumor, leading to tumor growth inhibition and prolonged survival in the mice. In some cases, complete responses (CRs) were observed, and mice that achieved CRs showed no tumor regrowth upon rechallenge, indicating the development of antitumor immunity and immunological memory.

Xenetic's DNase-based oncology platform is innovative in its approach to reducing NETs, which are expelled by activated neutrophils into the TME and blood, promoting cancer progression and immunosuppression. By decreasing the burden of NETs, Xenetic’s DNase I enhances the effectiveness of various cancer therapies, including immunotherapy, adoptive cell therapy, and chemotherapy, as shown in preclinical models.

Xenetic Biosciences aims to advance its DNase I program into clinical stages, focusing on its potential as an adjunctive therapy for pancreatic carcinoma and locally advanced or metastatic solid tumors. The company's goal is to improve the outcomes of existing cancer treatments by leveraging the unique capabilities of their DNase platform to target NETs effectively.