On November 21, 2024 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immune-oncology technologies addressing hard 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, NOV 21, 2024, View Source [SID1234648553]).
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The poster titled, "The synergistic action of DNase I and CAR T cells enhances the therapeutic efficacy of adoptive immunotherapy in the syngeneic murine metastasis model," was presented on behalf of the Company by Alexey Stepanov, PhD, Institute Investigator at The Scripps Research Institute, at the AACR (Free AACR Whitepaper) Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer, held November 17-20, 2024, in Boston.
"Xenetic’s proprietary DNase-based oncology platform continues to demonstrate encouraging potential across a number of cancer indications and therapy modalities where there remains significant unmet need. CAR T cell therapy is a promising approach for treating various malignancies however, it has so far shown benefit only in hematological cancers, so efficacy in solid tumors remains an important goal. There, its antitumor activity is often hindered by a hostile, immunosuppressive tumor microenvironment (TME), which, in turn, is very often characterized by the presence of tumor-associated cell-free DNA (cfDNA) in the form of neutrophil extracellular traps (NETs). This research underscores the critical role of the NETs in modulating CAR T cell efficacy and the potential of DNase I to improve therapeutic responses for patients as an adjunctive treatment. Highlighted by the results seen with the co-administration of DNase I with murine EGFR-CAR T cells, we believe this approach has the potential to prolong survival compared to treatment with CAR T cell monotherapy," commented Reid Bissonnette, Ph.D., Executive Consultant for Translational Research and Development at Xenetic. "We continue to be encouraged by the data demonstrated to date and look forward to further exploring the translational potential of this combinatorial approach in enhancing cancer treatment."
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
Co-administration of single injection of DNase I (10 mg/kg) with murine EGFR-CAR T cells demonstrated to significantly suppress metastatic tumor burden, decreases the number of metastatic foci, and substantially prolongs survival compared to the CAR T cell monotherapy group.
Degrading of NETs by DNase I increases the amount of tumor-infiltrating T and CAR T cells and reduces the immunosuppressive effects of the TME.
Tumor immune cell infiltrate analysis revealed that the CD8 population of tumor-infiltrating CAR T cells from the DNase I treated group have lower expression of PD-1 and TIM-3 exhaustion markers.
Xenetic continues to advance its DNase-based oncology program 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.