Soluble CD24 Protein Modulation of Immune Responses in Cancer Therapy
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Solution Overview
Problem
Current cancer immunotherapies, such as those targeting CTLA4 and PD-1/PD-L1, often cause immune-related adverse events (irAEs) due to breaches in self-tolerance, leading to inflammatory reactions and autoimmune responses, which can be severe and life-threatening, with limited effective treatments available to manage these adverse effects without compromising anti-cancer immunity.
Innovation Solution
Administration of a CD24 protein, which can be a mature human CD24 or its variant, to mitigate or prevent irAEs by modulating the host response to damage-associated molecular patterns (DAMPs), thereby reducing inflammatory cytokine production and autoimmune disease severity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cancer immunotherapy (anti-CTLA4, anti-PD-1/PD-L1) is administered to enhance anti-tumor immunity, then therapeutic efficacy against cancer is improved, but immune-related adverse events (irAEs) occur due to breaches in self-tolerance
Solution Approach 1:
The patent uses anti-CD25 antibodies (anti-il-2ralpha antibodies) as intermediary agents that specifically target and modulate the IL-2 signaling pathway. This selective intervention allows the therapy to dampen autoimmune responses mediated by IL-2 while preserving the broader anti-tumor immune activation, thus resolving the contradiction between therapeutic efficacy and irAE management
Solution Approach 2:
The patent changes the immunological parameter by selectively blocking the IL-2 receptor alpha chain (CD25), which is highly expressed on activated T cells and regulatory T cells. This parameter-specific intervention allows differential modulation of immune responses - reducing autoimmune pathology while maintaining anti-tumor immunity - thereby resolving the contradiction between efficacy and safety
2Reliability
If combination therapy with anti-CTLA4 and anti-PD-1/PD-L1 antibodies is used to improve therapeutic effect, then anti-tumor immunity is enhanced, but rates of grade 3 and grade 4 organ toxicity increase
Solution Approach 1:
The patent introduces anti-CD25 antibodies as a third intermediary agent that specifically targets the IL-2 signaling pathway. This selective intervention acts as a buffer that dampens the excessive immune activation and autoimmune responses caused by combination checkpoint blockade, allowing the maintenance of high therapeutic effect while reducing severe organ toxicity
Solution Approach 2:
The patent converts the harmful excessive immune activation and autoimmune responses (harm) into a beneficial outcome by using anti-CD25 antibodies to selectively modulate IL-2 signaling. The same IL-2 pathway that mediates autoimmune toxicity is repurposed as a therapeutic target to control irAEs, while the overall immune activation against tumor remains intact
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 protein effectively treats or prevents irAEs by discriminating between pathogen-associated and tissue damage signals, providing a negative regulation of inflammatory responses, thus reducing the severity of autoimmune reactions while preserving cancer immunotherapy efficacy.
Implementation Method 1
The CD24 protein effectively treats or prevents irAEs by discriminating between pathogen-associated and tissue damage signals, providing a negative regulation of inflammatory responses
Data Source
AI summary
The present invention relates to a CD24 protein for treating immune-related adverse events (irAEs) associated with cancer immunotherapy. Provided herein is a method of treating, mitigating, minimizing, or preventing immunerelated adverse events (irAEs) associated with a cancer immunotherapy by administering a CD24 protein to a subject in need thereof. The irAE may be diarrhea or another gastrointestinal disorder, pure red cell aplasia, microcytic anemia, lupus, autoimmune nephritism, autoimmune hepatitis, pneumonitis, myocarditis, pericarditis, endocrinopathy, Addison's disease, hypogonadism, Sjogren's syndrome, or type I diabetes. The CCD24 protein may comprise a mature human CD24 or a variant thereof.