On March 13, 2025 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immuno-oncology technologies addressing difficult to treat cancers, reported the presentation of preclinical data investigating the potential of co-administration of deoxyribonuclease I (DNase I) with chimeric antigen receptor (CAR) T cells in a syngeneic B16 melanoma murine model of lung metastasis (Press release, Xenetic Biosciences, MAR 13, 2025, View Source [SID1234651133]).
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The poster titled, "DNase I Intervention Enhances CAR-T Cell Therapy in Solid Tumors by Targeting Neutrophil Extracellular Traps in Metastatic Melanoma," was presented on behalf of the Company by Alexey Stepanov, PhD, Institute Investigator at The Scripps Research Institute, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Spring Scientific 2025 Cell Therapy Meeting being held March 12 – 14, 2025 in San Diego, CA and virtually.
"These findings further illuminate the crucial role of NETs in limiting CAR T cell function and underscore the potential of DNase I as an adjunctive treatment to improve patient responses to immunotherapies. We continue to be encouraged by the growing body of positive preclinical data and believe that our approach has the potential to prolong survival compared to treatment with CAR T cell monotherapy, including CAR T therapies directed against solid tumors, where there has been only limited activity to date. We are committed to advancing our DNase development program forward and further exploring the translational potential of this combinatorial approach, and to provide patients with a much-needed alternative treatment option that has the potential to address several unmet needs in cancer treatment," commented Reid Bissonnette, Ph.D., Executive Consultant for Translational Research and Development at Xenetic.
For the preclinical study, co-administration of DNase I with CAR T cells was investigated in a syngeneic B16 murine melanoma model of lung metastasis. Bioluminescent imaging of melanoma metastatic processes has shown that a single injection of DNase I (10 mg/kg) together with CAR T cells suppressed B16-EGFR lung metastasis at early stages in comparison to the vehicle control group and extended survival
Key Highlights
Using bioluminescent imaging, researchers observed that a single injection of DNase I (10 mg/kg) effectively suppressed B16-EGFR lung metastasis at early stages compared to vehicle controls. However, while DNase I demonstrated efficacy in reducing tumor growth, it did not significantly improve survival when administered alone.
The combination treatment of DNase I with murine EGFR-CAR T cells led to a marked suppression of tumor burden, a decrease in the number of metastatic foci, and substantial prolongation of survival compared to CAR T cell monotherapy. This therapeutic enhancement was associated with an increase in tumor-infiltrating T and CAR T cells, indicating improved immune engagement.
Analysis of the CD8 T cell population from DNase I-treated groups revealed a notable decrease in PD-1 and TIM-3 expression, markers of T cell exhaustion, suggesting that DNase I effectively mitigates the immunosuppressive effects of the tumor microenvironment (TME).
Xenetic continues to advance its DNase-based technology towards Phase 1 clinical development for the treatment of pancreatic carcinoma and other locally advanced or metastatic solid tumors. Preliminary preclinical studies evaluating the combinations of DNase I with chemotherapy and DNase I with immuno-therapies in colorectal cancer models as well as CAR-T therapy have been completed.