Xenetic presents preclinical data on DNase platform technology

Xenetic (XBIO) Biosciences announced the presentation of positive preclinical data. The poster titled, ” DNase I Targeting of Neutrophil Extracellular Traps Improves CTLA-4 Immune Checkpoint blockade in Models of MSS/MMRp CRC ,” was presented byReid Bissonnette, Ph.D., Executive Consultant for Translational Research and Development at Xenetic at the Society for Immunotherapy of Cancer 39 th Annual Meeting held on November 6-10, 2024, in Houston, Texas and virtually. For the preclinical study, mice were implanted with either CT26 or Colon26 cells, both mouse models of MSS/MMRp CRC. The mice were treated with anti-CTLA-4 and either daily or biweekly DNase I. Response was monitored by measuring tumor volume. Key Highlights: Data demonstrates beneficial effects of targeting NETs with systemic DNase I in models of primary tumor and metastatic CRC, improving the efficacy of CTLA-4 immune checkpoint blockade. Both published and newer data suggests that DNase I impedes neutrophil tumor infiltration, promotes CD4 and CD8 T cell infiltration, and enhances intratumoral T cell activation. DNase I plus -CTLA-4 combination therapy results in tumor growth inhibition, several CRs and enhanced survival in mice bearing CT26 or Colon26 MSS/MMRp CRC tumors. Dose response evaluations of DNase I combined with -CTLA-4, examining both route and frequency of administration was performed. DNase I plus -CTLA-4 combination therapy resulted in complete responses in mice bearing either CT26 or Colon26 tumors. Significantly, rechallenge of Colon26 and CT26 complete responder animals resulted in no tumor take or growth, suggesting that DNase I combined with -CTLA-4 promoted antitumor immunity and immunological memory. Xenetic’s DNase-based oncology platform is designed to target NETs, which are weblike structures composed of extracellular chromatin coated with histones and other proteins. In cancer, NETs are expelled by activated neutrophils into the TME and blood, thereby promoting cancer spread and local and systemic immunosuppression. Reduction of NETs burden via application of Xenetic’s proprietary recombinant human DNase I has been shown to improve efficacy of immunotherapy, adoptive cell therapy and chemotherapy in preclinical animal models.