On June 4, 2026 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 that its collaboration partner, PeriNess Ltd. (PeriNess), has informed the Company that it received formal approval from the Israeli Ministry of Health and the respective Institutional Review Board to conduct an exploratory clinical study of a combination systemic DNase I with anti-CD19 CAR T Cells in large B cell lymphoma (LBCL) patients. This approval follows positive preclinical results that demonstrated significant improvement of CAR T cell expansion and persistence and functionality when combined with DNase I. This combination therapy resulted in improved tumor control, delayed relapse and prolonged survival across multiple preclinical models of leukemia and lymphoma.
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Under the approved clinical study protocol, 12 LBCL patients with stable or progressive disease prior to lymphodepletion therapy are intended to be treated with CAR T cells targeting CD19 (tisagenlecleucel, axicabtagene ciloleucel, or lisocabtagene maraleucel) in combination with DNase I (50-ml IV infusion dose, 1.0 mg/kg IV on Days 0,3,6,10 and 15 after CAR T cells infusion). Clinical efficacy is intended to be evaluated by the Objective Response Rate (ORR) at 1 and 3 months post CAR T infusion, duration of response (DOR), disease control rate (DCR) and overall survival (OS) at 12 months post CAR T cells infusion. We believe the study has the potential for a translational component with a complex assessment of biomarker response and analysis of anti-CD19 CAR T expansion and persistence.
Dr. Ron Ram, Professor of Medicine and Head of the Bone Marrow Transplantation Unit at the Sourasky Center, has initiated the study as the principal investigator and all work is intended to be conducted at Sourasky Center in Israel.
"Progression of LBCL is the major obstacle for the success of CAR T therapies, with approximately 50-60% of the patients relapsing in the first year, and approximately 30-45% within 3 months after CAR T infusion, depending on the CAR T product used. While patients with partial or complete response before CAR T infusion have a 1-year progression free survival of approximately 60-80%, those with stable or progressive disease at the time of CAR T infusion have a dismal 1-year progression free survival of approximately 20-30%," commented Dr. Ram "Preclinical data generated over the last few years confirms that accumulation of cell-free chromatin and neutrophil extracellular traps (NETs) within the tumor microenvironment represents a general mechanism of CAR T-cell dysfunction through induction of exhaustion, immunosuppression and impaired expansion and this mechanism is targetable by DNase I. The goal of this clinical study is to improve clinical response by administering DNase I to abrogate the negative effects of cell-free chromatin and NETs on the performance of immune system and CAR T cells."
Alexey Stepanov, PhD, Institute Investigator at The Scripps Research Institute and a member of Xenetic’s Scientific Steering Committee, added, "CAR T cell treatment induces intensive tumor-cell death and inflammation within the tumor over a short period of time, resulting in massive release of cell-free chromatin and neutrophil extracellular traps (NETs) into the tumor microenvironment. This extracellular DNA burden acts as a major stress factor that accelerates CAR T cell dysfunction and exhaustion, creating a potent negative feedback loop that limits durable efficacy. DNase I disrupts this loop by degrading cell-free chromatin and NETs, thereby improving CAR T cell fitness, preserving cytotoxicity and functional persistence and reducing exhaustion markers, including PD-1, LAG-3, and TIM-3. In our preclinical models, these effects were associated with more durable tumor control following repeated tumor re-challenge, with no tumor regrowth observed in DNase I-treated animals under conditions where tumor progression occurred in the control group. Importantly, unlike conventional strategies that seek to improve CAR T cells primarily through additional cell engineering, our approach is designed to improve the battlefield itself by removing key extracellular barriers to CAR T cell function. We believe the planned study at Tel Aviv Sourasky Medical Center is particularly meaningful given the institution’s longstanding leadership in CAR T-cell therapy and immuno-oncology innovation, both in Israel and internationally. As a pioneer in the development, clinical validation and early adoption of advanced cellular therapies, Sourasky Center combines elite clinical expertise, cutting-edge translational research infrastructure and a proven ability to rapidly translate scientific discoveries into innovative patient treatments, making it an ideal institution to lead this exploratory clinical study."
(Press release, Xenetic Biosciences, JUN 4, 2026, View Source [SID1234666442])