Attenuated Salmonella IL-21 Secretion Vector for Stable Cancer Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing attenuated Salmonella strains used for cancer treatment are less viable and have a risk of converting to wild-type strains, causing sepsis, and there is a need to enhance immune stimulation and expression of therapeutic proteins like interleukin-21 for effective cancer therapy.
Innovation Solution
A recombinant expression vector is developed with flgM, interleukin-21, and flhDC genes operably linked to an inducible promoter, enhancing the expression and secretion of a flgM-IL-21 fusion protein using a type III secretion system in an attenuated Salmonella strain.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If attenuated Salmonella strain is used for cancer treatment, then tumor-attacking properties are maintained, but viability decreases and risk of converting to wild-type strain increases
Solution Approach 1:
The patent combines multiple functional genes (flgM, interleukin-21, flhDC) into a single recombinant expression vector that is integrated into the attenuated Salmonella strain. This merging approach allows the strain to simultaneously maintain attenuation for safety while expressing therapeutic proteins to enhance anti-cancer efficacy, resolving the contradiction between safety and productivity.
Solution Approach 2:
The recombinant expression vector serves multiple functions: it maintains the attenuated state of Salmonella for safety, expresses interleukin-21 for immune stimulation, and produces flgM-flhDC fusion protein for tumor targeting. This multi-functionality allows a single strain to address both safety concerns and therapeutic effectiveness.
2Reliability
If attenuated Salmonella strain is used for cancer treatment, then tumor-attacking properties are maintained, but immune stimulation capability decreases
Solution Approach 1:
The patent merges the interleukin-21 gene with the flgM and flhDC genes in the same recombinant expression vector. This ensures that the attenuated Salmonella strain simultaneously maintains tumor-targeting capability while producing interleukin-21 for enhanced immune stimulation, resolving the contradiction between tumor targeting and immune stimulation.
Solution Approach 2:
The recombinant expression vector acts as an intermediary carrier that delivers both tumor-targeting functions (flgM, flhDC) and immune-stimulating functions (interleukin-21) into the attenuated Salmonella strain, enabling the strain to perform multiple functions that would otherwise be mutually exclusive.
3Productivity
If recombinant expression vector with flgM-IL-21 fusion protein is expressed, then anticancer effects are enhanced, but protein secretion efficiency decreases
Solution Approach 1:
The patent merges the flgM gene (encoding a secretion signal peptide) with the interleukin-21 gene to create a fusion protein. The flgM portion serves as a secretion signal that directs the interleukin-21 protein to be efficiently secreted from the bacterial cell, thereby resolving the contradiction between enhancing anticancer efficacy and maintaining protein secretion efficiency.
Solution Approach 2:
The patent extracts and utilizes the secretion signal peptide function from the flgM gene and applies it to the interleukin-21 protein. By taking out the secretion function and separating it as a distinct functional element within the fusion protein, the system achieves efficient protein secretion while maintaining the full anticancer activity of interleukin-21.
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 recombinant vector significantly enhances the expression and secretion of flgM-IL-21, resulting in improved anticancer effects and stability, making the attenuated Salmonella strain an effective targeted therapeutic agent.
Implementation Method 1
enhancing the expression and secretion of a flgM-IL-21 fusion protein using a type III secretion system
Data Source
AI summary
The present disclosure relates to a recombinant expression vector for secretion of interleukin-21 and an attenuated Salmonella strain transformed therewith, and provides: a recombinant expression vector comprising an flgM gene and an interleukin-21 gene; an attenuated Salmonella strain transformed therewith; and a pharmaceutical composition for cancer treatment, comprising the attenuated Salmonella strain.