DEspR Antibody Control of NETosis and Neutrophil Tissue Injury
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Solution Overview
Problem
There is no therapy that can effectively stop or neutralize neutrophil-driven secondary tissue injury or NET-associated tissue injury without causing further damage or inducing new problems, particularly in conditions involving dysregulated activated PMNs.
Innovation Solution
The use of anti-DEspR antibodies or inhibitors that specifically bind to DEspR to block or reverse the prolonged lifespan of activated PMNs, thereby preventing or decreasing NET release and reducing tissue injury.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If activated PMNs are allowed to persist to kill bacteria and initiate wound healing, then antimicrobial activity and wound healing are improved, but secondary tissue injury and organ dysfunction worsen
Solution Approach 1:
The patent extracts and removes activated PMNs from the system using anti-DEspR antibodies that specifically bind to and clear dysregulated activated neutrophils. This extraction approach eliminates the harmful prolonged presence of activated PMNs that cause secondary tissue injury, while the timing and specificity of the antibody intervention ensures that antimicrobial function is preserved during the critical early phase of infection response.
Solution Approach 2:
The patent introduces anti-DEspR antibodies as an intermediary agent that mediates the selective removal of activated PMNs. These antibodies serve as a controlled intervention mechanism that can shut down excessive neutrophil activation without directly interfering with the neutrophil's antimicrobial functions, thereby resolving the contradiction between maintaining protective immunity and preventing tissue damage.
2Reliability
If NETosis is enhanced to trap and kill pathogens, then antimicrobial defense is improved, but direct tissue injury and vascular occlusion worsen
Solution Approach 1:
The patent applies extraction by removing NETosing neutrophils from the system using anti-DEspR antibodies. By specifically clearing NET+ activated PMNs, the patent eliminates the source of harmful NET deposition in tissues and vasculature while preserving the initial pathogen-trapping function that occurs during the controlled early phase of NETosis.
3Object-generated harmful factors
If activated PMNs are cleared rapidly to prevent tissue injury, then secondary tissue injury is reduced, but antimicrobial activity and wound healing may be compromised
Solution Approach 1:
The patent employs preliminary action by administering anti-DEspR antibodies at the onset of dysregulated neutrophil activation to prevent the development of harmful prolonged activation and secondary tissue injury. This timely intervention stops the vicious cycle before it causes significant damage, while the specificity of DEspR targeting ensures that essential wound healing processes are not disrupted.
Solution Approach 2:
The anti-DEspR antibody serves as a mediator that selectively intervenes in pathological neutrophil activation without broadly suppressing the immune response. By targeting specifically the dysregulated activated state through DEspR, the antibody preserves normal wound healing functions while eliminating harmful prolonged activation.
Data Source
AI summary
Described herein are methods and compositions relating to methods of inhibiting neutrophils, e.g., inhibiting NET release or NETosis, by means of a DEspR inhibitor, e.g., an anti-DEspR antibody reagent. In some embodiments, the methods can relate to the treatment of a disease, e.g., cancer or a disease wherein neutrophils; NETs; or NETosing or NETting neutrophils contribute to pathogenesis, chronicity, or worsening of disease. In some embodiments, the DEspR inhibitor can be a bi-specific reagent or an antibody-drug conjugate.