Attenuated Salmonella VC1 Secretion Vector for Safer Cancer Therapy

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Solution Overview

Problem

Existing attenuated Salmonella strains used for cancer treatment are less viable and pose a risk of converting to wild-type strains, causing sepsis, while also lacking sufficient immune stimulation and expression of anticancer substances.

Innovation Solution

A recombinant expression vector is developed with flgM, VC1, and flhDC genes operably linked to an inducible promoter, enhancing the expression and secretion of a fusion protein flgM-VC1 through a type III secretion system in an attenuated Salmonella strain.

Engineering Contradictions & Design Principles

VSEngineering 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

Engineering Contradiction:

ImprovesafetyVSAvoidviability

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent combines multiple functional genes (flgM, VC1, flhDC) into a single recombinant expression vector that is integrated into the attenuated Salmonella strain. This merging approach allows simultaneous achievement of tumor targeting, immune stimulation, and anticancer substance expression while maintaining strain attenuation, thereby resolving the contradiction between safety and viability.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The attenuated Salmonella strain is engineered to perform multiple functions: tumor site accumulation, immune system stimulation, and secretion of anticancer substances (VC1). The recombinant expression vector enables the strain to simultaneously fulfill these diverse roles, improving overall therapeutic effectiveness without compromising safety.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If attenuated Salmonella strain is used for cancer treatment, then tumor-attacking properties are maintained, but immune stimulation capability decreases

Engineering Contradiction:

Improvetumor-attacking capabilityVSAvoidimmune stimulation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent merges the VC1 gene (encoding anticancer substance) with the flgM and flhDC genes in a single recombinant expression vector. This integration ensures that the attenuated Salmonella strain simultaneously maintains tumor-attacking properties while effectively stimulating immune response and delivering anticancer substances to tumor sites.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The recombinant expression vector acts as an intermediary carrier that delivers multiple functional components (flgM, VC1, flhDC) into the attenuated Salmonella strain. This intermediary structure enables the strain to effectively stimulate immune response and attack tumors without the harmful effects of wild-type Salmonella.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If recombinant expression vector with flgM-VC1 fusion protein is expressed, then secretion efficiency is improved, but gene structure complexity increases

Engineering Contradiction:

Improvesecretion efficiencyVSAvoidgene structure

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent merges the flgM and VC1 genes into a single fusion protein construct (flgM-VC1) within the recombinant expression vector. This merging strategy improves secretion efficiency by creating a chimeric protein that utilizes the type III secretion system while maintaining manageable gene structure complexity through integrated design.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent employs an inducible promoter system that allows dynamic control of flgM-VC1 expression. By changing the expression parameter from constitutive to inducible, the system achieves high secretion efficiency when needed while maintaining simpler gene structure during non-expression phases.

Inventive Principle:

Principle #35Parameter changes

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-VC1, leading to effective immune stimulation and anticancer effects with improved stability and safety.

Implementation Method 1

enhancing the expression and secretion of a fusion protein flgM-VC1 through a type III secretion system in an attenuated Salmonella strain

Methodology Applied

Scientific EffectType III secretion system:

Data Source

PatentUS20260021146A1Recombinant expression vector for VC1 secretion, and attenuated salmonella strain transformed therewith

Publication Date: 2026.01.22 THE IND & ACADEMIC COOP IN CHUNGNAM NAT UNIV (IAC)

AI summary

The present disclosure relates to a recombinant expression vector for secretion of a VC1 protein and an attenuated Salmonella strain transformed therewith, and provides: a recombinant expression vector comprising an flgM gene, a VC1 gene, and an flhDC gene; an attenuated Salmonella strain transformed therewith; and a pharmaceutical composition for cancer treatment, comprising the attenuated Salmonella strain.