DNase Immunomodulation of Tumor Microenvironment Resistance
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Solution Overview
Problem
Current cancer treatments, particularly those using immune checkpoint modulators, have limited effectiveness and are associated with significant immune-related adverse events, while elevated levels of circulating cell-free DNA contribute to tumor progression and chemotherapy resistance.
Innovation Solution
Administering a deoxyribonuclease (DNase) enzyme to modulate the immunosuppressive tumor cell microenvironment and tumor-associated microbiome, potentially combined with immune checkpoint modulators, to enhance tumor cell killing and reduce adverse events.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint modulators are used to treat cancer, then tumor cell killing is enhanced, but immune-related adverse events increase and treatment efficacy is limited
Solution Approach 1:
DNase I acts as an intermediary agent that degrades extracellular DNA in the tumor microenvironment, thereby modulating the immune response. This mediator reduces the immunosuppressive effects of DNA while enhancing the efficacy of immune checkpoint modulators, and can also mitigate immune-related adverse events by regulating the overall immune activation level.
2Quantity of substance
If high doses of DNase protein are administered systemically, then circulating cell-free DNA levels are reduced, but treatment complexity and dosage requirements increase
Solution Approach 1:
The patent combines DNase I treatment with immune checkpoint modulator therapy in a coordinated regimen. The DNase I is administered at specific dosages and schedules to preemptively reduce extracellular DNA burden before or during immunotherapy, thereby enhancing treatment efficacy without requiring excessively high doses of either agent alone.
3Reliability
If DNase enzyme is combined with immune checkpoint modulators, then treatment efficacy is improved, but treatment protocol complexity increases
Solution Approach 1:
The patent merges DNase I therapy with immune checkpoint modulator therapy into a unified treatment protocol. This combination leverages the complementary mechanisms of action: DNase I degrades extracellular DNA to reduce immunosuppression and enhance immune cell function, while immune checkpoint modulators release brakes on the immune system. The synergistic effect improves treatment efficacy for cancers that are resistant to single-agent therapy.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enhances tumor cell killing by cytotoxic CD8 T cells and NK cells, reduces tumor-associated macrophages and neutrophils, and mitigates immune-related adverse events, improving treatment efficacy and patient outcomes.
Implementation Method 1
administering a deoxyribonuclease (DNase) enzyme to modulate the immunosuppressive tumor cell microenvironment
Data Source
AI summary
The invention relates to methods for immunomodulation of immunosuppressive tumor cell microenvironment and prevention of tumor microbiome effects through multiple pathways with DNase enzyme therapy. Methods for immunomodulation of immunosuppressive tumor cell microenvironment comprising administering an effective amount of deoxyribonuclease (DNase) enzyme, either alone or in combination with other immunomodulating agent.