CD24-Expressing Cell-Derived Particles for Cytokine Storm Therapy
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Solution Overview
Problem
Current treatments for cytokine storm syndrome, coronavirus infection, and tissue damage associated with inflammation are inadequate, particularly for severe cases like ARDS, which are characterized by high mortality rates and lack effective therapeutic options.
Innovation Solution
A composition comprising cell-derived particles presenting heterologous CD24, which are derived from non-cancerous cells and are substantially devoid of intact cells, is administered to treat or prevent cytokine storm syndrome, coronavirus infection, and tissue damage associated with inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for cytokine storm syndrome and ARDS, then standard therapeutic protocols are applied, but mortality rates remain high at 20-40% and no effective treatment is available
Solution Approach 1:
The patent uses CD24-expressing cell-derived particles as an intermediary therapeutic agent that mediates between the immune system and the pathological cytokine storm. These particles bind to DAMPs and modulate immune responses through Siglec-10, serving as a bridge to control the harmful inflammatory cascade without directly attacking the virus or cytokines.
Solution Approach 2:
The invention converts the harmful excessive immune response (cytokine storm) into a beneficial controlled response by using CD24 particles to selectively modulate the immune system. The same immune mechanisms that cause damage are redirected and regulated to protect the patient while maintaining necessary immune function.
2Reliability
If the body's immune response is activated to fight infection, then pathogen clearance is achieved, but excessive pro-inflammatory cytokine production leads to tissue damage and multi-organ failure
Solution Approach 1:
The CD24-expressing particles exhibit local quality by selectively interacting with specific immune components (DAMPs and Siglec-10) rather than broadly suppressing the entire immune system. This localized modulation allows the immune system to maintain its defensive capabilities while specifically regulating the harmful inflammatory pathway.
Solution Approach 2:
The invention changes the parameter of immune response intensity by introducing CD24 particles that shift the balance from excessive pro-inflammatory cytokine production to a regulated state. This parameter change occurs through the CD24-Siglec-10 interaction pathway, which down-regulates NFκB activation and controls cytokine release.
3Reliability
If intact cells are used as therapeutic agents, then cellular functions are preserved, but safety concerns arise from potential uncontrolled proliferation and immune rejection
Solution Approach 1:
The patent extracts the therapeutic functionality (CD24 expression and particle formation) from intact cells by using cell-derived particles that are substantially devoid of intact cells. This extraction removes the safety risks associated with live cell therapy while preserving the beneficial immunomodulatory functions of CD24-expressing particles.
Solution Approach 2:
The cell-derived particles function as disposable therapeutic agents that perform their immunomodulatory role and are then cleared from the body, eliminating the long-term safety concerns associated with persistent cellular therapies. The particles provide temporary controlled intervention without the risks of uncontrolled proliferation.
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 CD24-expressing cell-derived particles effectively suppress hyper-immune activity, inhibit NFκB activation, and down-regulate exaggerated host responses, thereby reducing cytokine levels and lung damage in ARDS, and demonstrating a high safety profile and clinical efficacy in Phase I clinical trials.
Implementation Method 1
CD24 also plays an important role in controlling homeostatic proliferation of T cells and can negatively regulate inflammation. It was previously shown that CD24 is a dominant innate immune checkpoint, 'do not eat me signal'.
Implementation Method 2
CD24's link to DAMPs prevents them from binding to the TLRs, therefore inhibiting the NFκB pathway. At the same time, the CD24-Siglec-10 axis negatively regulates the activity of NFκB through Immunoreceptor Tyrosine-based Inhibition Motif domains associated with SHP-1
Data Source
AI summary
A method of producing cell derived particles is disclosed. The method comprising isolating cell-derived particles from a biological sample comprising cells modified to present CD24 so as to obtain a preparation of the cell-derived particles substantially devoid of intact cells. Cell derived particles, a culture medium and a cell culture are also disclosed.