Engineered Lactic Acid Bacteria for Therapy-Induced Enteropathy
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Solution Overview
Problem
Current treatments for therapy-induced enteropathy, particularly immune checkpoint inhibitor-induced enterocolitis and radiation-induced enteropathy, lack effective and targeted therapeutic strategies, as existing methods are based on clinical symptoms rather than objective markers, and there is limited evidence for optimal treatment timing and duration, leading to potential negative impacts on cancer therapy efficacy.
Innovation Solution
Administration of genetically engineered lactic acid bacteria (LAB) that express proteins promoting inflammation resolution and wound healing, such as CXCL12, CXCL17, Ym1, and TGF-β, to modulate local immune responses and reduce damage in the gastrointestinal tract.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If TNF inhibitor infliximab is administered to treat ICI-induced enterocolitis, then inflammation is reduced, but the effectiveness of ICI cancer therapy is compromised
Solution Approach 1:
The patent applies local quality by using engineered lactic acid bacteria that deliver anti-inflammatory proteins (such as IL-10, TGF-β, or EBI3) specifically to the gastrointestinal tract where enterocolitis occurs. This localized delivery reduces systemic immune suppression while providing targeted anti-inflammatory action, thereby maintaining ICI effectiveness in cancer therapy while treating GI inflammation.
Solution Approach 2:
The patent uses engineered lactic acid bacteria as an intermediary carrier to deliver anti-inflammatory proteins directly to the site of inflammation in the GI tract. These bacteria act as mediators that bridge the need for inflammation control and the need to preserve ICI effectiveness, avoiding direct administration of systemic immunosuppressants like infliximab.
2Object-affected harmful factors
If systemic corticosteroids are administered to treat therapy-induced enteropathy, then inflammation is suppressed, but cancer therapy efficacy is reduced due to systemic immune suppression
Solution Approach 1:
The patent employs local quality by engineering lactic acid bacteria to deliver anti-inflammatory proteins specifically to the gastrointestinal tract. This localized approach provides anti-inflammatory effects where needed while avoiding systemic immune suppression, thereby preserving cancer therapy efficacy unlike systemic corticosteroids.
Solution Approach 2:
The engineered lactic acid bacteria are administered orally and self-deliver the anti-inflammatory proteins to the GI tract through their natural colonization and metabolic activities. This self-service delivery mechanism eliminates the need for systemic administration and associated systemic side effects.
3Reliability
If combination ICI therapy is administered to improve cancer control, then tumor suppression is enhanced, but the risk of immune-mediated adverse events including enterocolitis increases
Solution Approach 1:
The patent converts the harmful effect of excessive immune activation (which causes enterocolitis) into a benefit by using the same activated immune system to fight cancer, while simultaneously using engineered bacteria to deliver anti-inflammatory proteins that selectively dampen GI tract inflammation. This allows combination ICI therapy to maintain its anti-tumor effectiveness while reducing adverse events.
Solution Approach 2:
The patent changes the local immune parameter in the GI tract by delivering anti-inflammatory proteins through engineered bacteria, thereby altering the balance between immune activation (beneficial for cancer) and immune-mediated damage (harmful in enterocolitis). This parameter change allows combination therapy to proceed with reduced toxicity.
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 engineered LAB effectively reduce disease activity, crypt damage, and epithelial loss, inhibit fibrosis, and prevent colon shortening in therapy-induced enteropathy, while maintaining cancer therapy efficacy by local immunomodulation without systemic immune suppression.
Implementation Method 1
lactic acid bacteria which have been engineered recombinantly to express a therapeutic protein capable of promoting resolution of inflammation and/or wound healing
Data Source
AI summary
The present invention provides lactic acid bacteria (LAB) which have been engineered to express a therapeutic protein capable of promoting resolution of inflammation and/or wound healing for use in treating or preventing therapy-induced enteropathy in a human or animal subject.