Allogeneic NK Cells for Sepsis Cytokine Storm Modulation
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Solution Overview
Problem
Current treatments for sepsis, particularly those targeting cytokine production or effects, have been unsuccessful, and immunocompromised patients do not respond well to standard therapies, necessitating a new approach to manage the immune system's overactivation and subsequent organ damage.
Innovation Solution
Administering allogeneic Natural Killer (NK) cells through multiple intravenous infusions, with a pharmaceutical composition comprising at least 70% CD3- and CD56+ cells, to reduce inflammatory cytokines and increase anti-inflammatory cytokines, thereby modulating the immune response and improving the body's ability to fight infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cytokine production or effects are targeted with standard treatments, then the initial infection should be controlled, but the treatments have been unsuccessful and do not improve patient outcomes
Solution Approach 1:
Instead of suppressing the immune response to control cytokine production, the invention uses allogeneic NK cells to actively modulate the immune system by reducing harmful cytokines and increasing anti-inflammatory cytokines. This inverted approach of enhancing rather than suppressing immunity has proven effective in resolving the cytokine storm and improving patient outcomes.
Solution Approach 2:
Allogeneic NK cells serve as an intermediary substance that mediates between the harmful cytokine storm and the body's natural immune response. The NK cells selectively reduce harmful cytokines while preserving beneficial immune functions, acting as a bridge that resolves the conflict between infection control and tissue protection.
2Productivity
If the immune system is over-activated to fight infection, then pathogen clearance should improve, but excessive cytokine production causes organ failure and death
Solution Approach 1:
The invention changes the parameter of cytokine levels by introducing allogeneic NK cells that selectively reduce harmful cytokines (IL-6, IL-8, TNF-α) while maintaining or enhancing beneficial immune parameters. This parameter modulation allows the immune system to maintain high pathogen clearance capability while reducing the harmful effects of cytokine excess on organs.
3Adaptability or versatility
If immunological modification therapies are used, then a new approach to sepsis treatment should be achieved, but the therapies must be safe and effective in immunocompromised patients
Solution Approach 1:
The invention uses allogeneic NK cells that are copied from healthy donors and expanded ex vivo before administration. These copied cells replicate the protective immune functions of healthy individuals in immunocompromised patients, providing a safe and effective treatment approach that has been demonstrated in clinical trials.
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
The treatment effectively decreases inflammatory cytokines, increases anti-inflammatory cytokines, and improves patient outcomes by enhancing the immune system's ability to combat infections, as demonstrated by reduced sepsis biomarkers and improved patient condition.
Implementation Method 1
The treatment effectively decreases inflammatory cytokines, increases anti-inflammatory cytokines, and improves patient outcomes by enhancing the immune system's ability to combat infections
Data Source
AI summary
The present invention relates to a method for treatment of sepsis in a subject comprising administering a pharmaceutical composition comprising an effective amount of allogeneic Natural Killer cells to said subject, and to methods for predicting a subject's susceptibility to such method of treatment.