Viral Vector Encoding TLR5 and Flagellin for Tumor Immunity

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Solution Overview

Problem

Current cancer immunotherapy approaches using Toll-like receptor 5 (TLR5) agonists face limitations due to rare expression of functional TLR5 in tumors and systemic administration leading to non-specific immune activation, necessitating a method for autocrine activation of TLR signaling in tumor or infected cells to attract immune responses specifically.

Innovation Solution

A vector comprising nucleic acids encoding a secreted form of TLR5 and its agonist, flagellin, is used to transduce tumor cells, enabling local production of TLR5 and flagellin, thereby recruiting innate and adaptive immune responses to tumors or infected cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If TLR5 agonist is administered systemically, then immune response is activated, but the response becomes unfocused and not tumor-specific

Engineering Contradiction:

Improvetumor-specific immune responseVSAvoidsystemic administration

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent employs local gene therapy delivery of TLR5 agonist directly to tumor tissue, creating a localized concentration gradient that activates immune response specifically at the tumor site while minimizing systemic exposure. This spatially differentiated distribution resolves the contradiction between achieving reliable tumor-specific response and avoiding unfocused systemic activation.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent introduces tumor-associated antigens as intermediaries that link the TLR5 agonist activation to tumor-specific immune recognition. The antigens serve as mediators that direct the activated immune response specifically toward tumor cells expressing these antigens, thereby achieving focused tumor-specific immunity rather than generalized systemic activation.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If TLR5 agonist is used for cancer immunotherapy, then antitumor effect is induced, but applicability is limited to tumors expressing functional TLR5

Engineering Contradiction:

Improveantitumor effectVSAvoidapplicability to different tumors

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the immunotherapy approach into two independent components: TLR5 agonist delivery and tumor antigen presentation. This segmentation allows the therapy to be applied to any tumor type by simply identifying and incorporating tumor-specific antigens, rather than requiring all tumors to express functional TLR5. The modular design enhances versatility across different tumor types while maintaining reliable antitumor effects.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a universal immunotherapy platform based on TLR5 agonist activation that can be adapted to treat multiple tumor types through the inclusion of various tumor-associated antigens. The core TLR5 activation mechanism serves multiple tumor types universally, while the antigen component provides tumor-type specificity, achieving both broad applicability and targeted effectiveness.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If tumor cells are targeted for immune recognition, then effective immune response is achieved, but tumors use mechanisms to escape immune recognition

Engineering Contradiction:

Improveimmune recognitionVSAvoidtumor escape mechanisms

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by using TLR5 agonist to pre-activate immune cells and enhance their recognition capabilities before tumor cells can execute escape mechanisms. The pre-activated immune cells are primed to overcome tumor evasion strategies, establishing immune recognition before the tumor can respond with escape mechanisms such as antigen downregulation or immune suppressive microenvironment creation.

Inventive Principle:

Principle #10Preliminary action

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

This approach effectively induces NF-κB apoptosis pathway activation, specifically targeting and killing cancer cells or infected cells with minimal systemic immune activation, enhancing tumor-specific immune response and treatment efficacy.

Implementation Method 1

A vector comprising a first and second nucleic acid, wherein the first nucleic acid encodes a toll-like receptor and the second nucleic acid encodes a toll-like receptor agonist

Methodology Applied

Scientific EffectGene expression:

Implementation Method 2

This approach effectively induces NF-κB apoptosis pathway activation, specifically targeting and killing cancer cells or infected cells

Methodology Applied

Scientific EffectNF-κB apoptosis pathway activation:

Data Source

PatentUS9205095B2Viral vector encoding a toll-like receptor and encoding a toll-like receptor agonist

Publication Date: 2015.12.08 HEALTH RESEARCH INC

AI summary

The present invention is directed to methods and agents used for treating cancer or infectious diseases by providing toll-like receptors such as toll-like receptor 5 (TLR-5) in combination with providing a toll-like receptor agonists such as flagellin resulting in a cis and in-trans effect that recruits cells involved in both the innate (cis effect) and adaptive (trans effect) immune response to specifically kill cancer cells and cells infected with a pathogen via the NF-κB apoptosis pathway.