Parenterally injecting bovine pancreatic DNAse to destroy extracellular DNA in systemic blood circulation of cancer patient slow down malignancy; treating lung carcinomas
Inventors
Genkin, Dmitry Dmitrievich • Tets, Viktor Veniaminovich • Tets, Gregory Viktorovich
Assignees
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Publication Number
US-7612032-B2
Publication Date
2009-11-03
Expiration Date
Abstract
A method to treat solid tumors and other oncological diseases consists of parenterally injecting an agent which destroy's blood's extracellular DNA into the systemic blood circulation of a cancer patient to slow down malignant. The agent is embodied in the form of a DNAse enzyme and, more particularly, as a bovine pancreatic DNAse. Doses from 50,000-250,000,000 Kunz units/day are injected for 5-360 days. A binding agent or an agent that modifies the chemical composition of the blood extracellular DNA is additionally injected into the blood. This modifying agent is preferably an enzyme-ribonuclease.
Core Innovation
The disclosed invention provides a method of treating lung carcinoma, and malignant and low differentiated lymphomia, by introducing a treatment agent into a circulating blood system of a cancer patient diagnosed with at least one of the said cancers and diseases. The treatment agent destroys extracellular DNA in the blood of the patient, where the treatment agent used to destroy the extracellular DNA is a DNase enzyme. The method is characterized by ensuring that blood plasma DNA-hydrolytic activity measured in blood plasma exceeds 150 Kunitz units per liter of plasma during more than 12 hours in total within 24 hours.
A central aspect of the method is selecting a DNase enzyme capable of degrading extracellular DNA, including high-molecular fractions, through systemic administration. The description emphasizes maintaining plasma DNA-hydrolytic activity and includes DNase administration as either bovine pancreatic DNase and/or human recombinant DNase 1, identified as Dornase alpha (Domase alpha). The disclosed regimens include continuous administration duration constraints, with durations extending beyond 48 hours, and treatment periods described as spanning from 5 to 360 days.
The disclosed method further includes optional administration of agents that act on extracellular DNA beyond DNase. Specifically, the document describes introducing into the blood system a binding agent that binds extracellular DNA, where the binding agent is anti-DNA antibodies, and describes adding ribonucleases/proteases having extracellular DNA modifying activity. The combination is described as enhancing extracellular DNA degradation and supporting antitumor outcomes in the stated experimental settings.
Claims Coverage
The disclosure includes one independent claim covering a DNase-based systemic treatment of lung carcinoma and malignant and low differentiated lymphomia, with a plasma DNA-hydrolytic activity threshold as a key functional requirement; dependent claims further refine the timing, DNase sources/variants, dosage/time windows, and an optional anti-DNA antibody binding step.
Plasma DNA-hydrolytic activity exceedance window for DNase treatment
Introducing a treatment agent into a circulating blood system of a cancer patient, wherein the treatment agent destroys extracellular DNA in the blood and wherein the treatment agent used to destroy the extracellular DNA is a DNase enzyme, and wherein the treatment agent is administered in doses and regiments which provide blood plasma DNA-hydrolytic activity (measured in blood plasma) to exceed 150 Kunitz units per liter of plasma during more than 12 hours in total within 24 hours.
Continuous regimen duration
Administering the doses on a continuously executed regimen schedule for no less than 48 hours.
Bovine pancreatic DNase regimen
Using bovine pancreatic DNase administered parenterally in daily doses from 50,000 Kunitz units to 250,000,000 Kunitz units for 5 to 360 days to destroy extracellular DNA.
Human recombinant DNase variant
Using human recombinant DNase.
Human recombinant DNase 1 (Dornase alpha/Domase alpha) dosing and duration
Parenterally introducing human recombinant DNase 1 (Domase alpha) at 1.15 mg/kg to 500 mg/kg body weight daily for 5 to 360 days.
Anti-DNA antibody binding agent step
Introducing a binding agent into the blood system that binds extracellular DNA, wherein the binding agent is anti-DNA antibodies.
Across the independent claim and its dependents, the inventive coverage centers on systemic DNase-mediated destruction of extracellular DNA with a specified blood plasma DNA-hydrolytic activity threshold within a 24-hour window, further constrained by continuous administration duration and refined by DNase source/variant and dosing/timing, with an optional anti-DNA antibody binding-agent step.
Stated Advantages
Decreases extracellular DNA levels through DNase-mediated extracellular DNA destruction.
Maintains blood plasma DNA-hydrolytic activity above 150 Kunitz units per liter for more than 12 hours in total within 24 hours.
Provides tumor regression/antitumor effects as described in experimental settings.
Documented Applications
Treatment of lung carcinoma.
Treatment of malignant low differentiated lymphomia.
Use in clinical examples described for lung carcinoma.
Use in malignant low differentiated lymphoma with spleen/portal vein/liver metastases as described.
Preclinical tumor models described as including Erlich carcinoma and Lewis lung carcinoma.
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