TH17-Inducing Adjuvants Using TLR Agonists and Apoptotic Cells

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Solution Overview

Problem

Current methods for inducing effective immune responses in mucosal tissues face challenges, particularly in regulating TH17 responses, as they are associated with both protective immunity and autoimmune diseases, and existing mucosal adjuvants like cholera toxin are toxic and inefficient.

Innovation Solution

The development of compositions and methods involving microbe-infected apoptotic cells and TH17-inducing dendritic cells that secrete IL-6 and TGF-β, or combinations of TLR agonists and apoptotic cell-associated agents to induce or inhibit TH17 responses, allowing for targeted immune modulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cholera toxin is used as a mucosal adjuvant, then immune response induction is improved, but toxicity increases

Engineering Contradiction:

Improveimmune response inductionVSAvoidtoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and isolates the beneficial adjuvant properties from apoptotic cells and TLR agonists, separating them from the toxic effects of traditional adjuvants like cholera toxin. The composition uses specific biological components (apoptotic cells, TLR agonists) that can be precisely controlled to achieve immune stimulation without the uncontrolled toxicity of bacterial toxins.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the chemical and biological parameters of the adjuvant system by using apoptotic cells and TLR agonists instead of cholera toxin. This parameter change allows for precise control of immune response induction while avoiding the toxicity issues associated with traditional bacterial adjuvants.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If TH17 responses are induced for protective immunity, then mucosal immunity is improved, but autoimmune disease risk increases

Engineering Contradiction:

Improvemucosal immunityVSAvoidautoimmune disease

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent employs a feedback mechanism where the composition includes components that can regulate and control the TH17 response. The apoptotic cells and TLR agonists provide controlled stimulation that can be modulated to achieve protective immunity while preventing excessive activation that would lead to autoimmune pathology.

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The patent changes the regulatory parameters of TH17 responses by using controlled apoptotic cell stimulation and TLR agonist combinations. This allows for precise control of the immune response intensity and duration, achieving protective mucosal immunity while maintaining safety margins below the threshold for autoimmune disease induction.

Inventive Principle:

Principle #35Parameter changes

3Ease of operation

If protein antigens are administered via mucosal route, then vaccine delivery is simplified, but immunogenicity decreases

Engineering Contradiction:

Improvevaccine deliveryVSAvoidimmunogenicity

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent introduces apoptotic cells and TLR agonists as intermediary components that bridge the gap between simple mucosal delivery and effective immunogenicity. These intermediaries act as adjuvants that enhance the immune response to protein antigens administered via the mucosal route, overcoming the inherent weakness of mucosal protein delivery.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite vaccine composition that combines protein antigens with apoptotic cells and TLR agonists. This composite formulation maintains the ease of mucosal delivery while significantly enhancing immunogenicity through the synergistic effects of the combined components.

Inventive Principle:

Principle #40Composite materials

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

These approaches effectively induce TH17 responses for vaccine applications and treat autoimmune diseases by precisely regulating immune reactions, avoiding the toxicity issues of traditional adjuvants.

Implementation Method 1

an isolated TH17-inducing dendritic cell (DC) that secretes interleukin-6 (IL-6) and transforming growth factor beta (TGF-β)

Methodology Applied

Scientific EffectCytokine secretion:

Implementation Method 2

combinations of TLR agonists and apoptotic cell-associated agents to induce or inhibit TH17 responses

Methodology Applied

Scientific EffectToll-like receptor activation:

Data Source

PatentUS9233154B2T-helper cell type 17 lineage-specific adjuvants, compositions and methods

Publication Date: 2016.01.12 MT SINAI SCHOOL OF MEDICINE

AI summary

The present invention relates to compositions and methods for the modulation of TH17 responses. The invention provides compositions for the induction of TH17 responses containing a TLR agonist and an apoptotic cell-associated agent or containing a microbe-infected apoptotic cell. The compositions of the present invention may also contain dendritic cells capable of inducing TH17 responses. In other embodiments, the invention provides compositions for the inhibition of TH17 responses containing one or more blocking agents. Methods and compositions for the modulation of TH17 responses and for the treatment of TH17-associated diseases and for cancer are also provided.