Nfkbiz mRNA Stem-Loop Disruption for Solid Tumor Immunostimulation
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Solution Overview
Problem
Current cancer treatments, such as immune checkpoint inhibitors and CAR T-cell therapy, have limited efficacy against solid tumors, necessitating a novel approach to enhance immune cell activity against cancer cells.
Innovation Solution
A composition that disrupts specific stem-loop structures in the 3' untranslated region of Nfkbiz mRNA to increase expression of IκBζ, thereby stimulating immune cells to enhance cytotoxic activity against cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors or CAR T-cell therapy are used for cancer treatment, then immune response is activated, but efficacy against solid tumors remains insufficient
Solution Approach 1:
The invention changes the molecular parameter by disrupting the stem-loop structure in the 3' UTR of Nfkbiz mRNA, which prevents Regnase-1 binding and degradation. This parameter change leads to increased IκBζ protein expression levels, thereby enhancing immune cell cytotoxic activity against solid tumors and resolving the contradiction between general immune activation and solid tumor effectiveness
Solution Approach 2:
The invention introduces an intermediary substance (e.g., antisense oligonucleotide, small molecule) that specifically binds to the stem-loop structure of Nfkbiz mRNA to prevent Regnase-1-mediated degradation. This intermediary acts as a bridge between the existing immune checkpoint inhibitors/CAR T-cell therapy and the desired enhanced anti-tumor effect, allowing the combination to overcome solid tumor resistance
2Stability of the object's composition
If Regnase-1 degrades Nfkbiz mRNA to suppress excessive immune responses, then immune homeostasis is maintained, but Nfkbiz expression is suppressed reducing immune cell cytotoxicity
Solution Approach 1:
The invention extracts or removes the stem-loop structure element from the Nfkbiz mRNA that serves as the binding site for Regnase-1. By taking out this specific structural element through disruption, the patent prevents Regnase-1 from recognizing and degrading the mRNA, thereby extracting the problematic interaction while preserving immune homeostasis mechanisms and increasing Nfkbiz expression
Solution Approach 2:
The invention converts the harmful effect of Regnase-1-mediated mRNA degradation into a beneficial outcome. By disrupting the stem-loop structure, the patent transforms the previously harmful degradation pathway into an opportunity to stabilize Nfkbiz mRNA, increase IκBζ expression, and enhance anti-tumor immunity while maintaining overall immune regulation
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 composition induces immunostimulation, allowing for effective cancer treatment by boosting the immune system's ability to target and destroy cancer cells.
Implementation Method 1
disruption of a specific stem-loop structure among them suppresses degradation of Nfkbiz mRNA by Regnase-1 and Regnase-3
Implementation Method 2
Regnase-1 recognizes a stem-loop structure in the 3′ untranslated region (3′ UTR) of a mRNA and degrades the mRNA
Implementation Method 3
IκBζ binds to NF-κB subunit p50, enhances transcription by chromatin remodeling
Implementation Method 4
enhances transcription by chromatin remodeling
Implementation Method 5
stimulates immune cells to enhance cytotoxic activity against cancer cells
Data Source
AI summary
The disclosure provides a composition for treating cancer comprising at least one substance that disrupts a stem-loop structure in the 3′ untranslated region of an Nfkbiz mRNA, and methods use of thereof.