Bacterial Compositions for CD8+ T-Cell Induction

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Solution Overview

Problem

Current approaches to modulating the human microbiota for immune system manipulation, such as cancer immunotherapy and vaccine responses, are limited and often ineffective, particularly in elderly populations and those with microbiota modifications leading to infectious, inflammatory, and metabolic diseases.

Innovation Solution

Compositions of purified bacterial strains, including Fusobacterium ulcerans, Eubacterium limosum, Bacteroides dorei, and Bacteroides uniformis, are administered to induce and proliferate CD8+ T cells, enhancing immune responses through interferon gamma production, thereby treating infectious diseases and cancers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional approaches (antibiotics, prebiotics, probiotics, fecal transplants) are used to modulate microbiota, then some immune modulation effect is achieved, but they have limitations and potential adverse effects

Engineering Contradiction:

Improveeffectiveness of immune modulationVSAvoidadverse effects of microbiota modification

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the parameter of bacterial composition by identifying and administering a specific combination of four bacterial strains (Fusobacterium ulcerans, Eubacterium limosum, Bacteroides dorei, and Bacteroides uniformis) in defined ratios. This specific parameter configuration produces IFN-gamma producing CD8+ T cells without the adverse effects associated with conventional microbiota modulation approaches.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If cancer immunotherapy is administered, then survival rates improve for some patients, but a large percentage of patients do not respond

Engineering Contradiction:

Improveresponse rate to cancer immunotherapyVSAvoidapplicability across different patient populations

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention applies preliminary action by administering the bacterial composition before or in conjunction with cancer immunotherapy to pre-condition the immune system. The bacterial strains prime the immune system to generate IFN-gamma producing CD8+ T cells, which enhances subsequent response to cancer immunotherapy interventions.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If microbiota modification is performed to treat diseases, then immune responses are modulated, but tolerance against harmless antigens is lost leading to inflammatory responses

Engineering Contradiction:

Improveimmune response modulationVSAvoidexcessive inflammatory responses

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The invention applies local quality by targeting specific bacterial strains with particular properties that induce desired immune responses (IFN-gamma producing CD8+ T cells) without triggering excessive inflammation. Each of the four bacterial strains contributes specific local qualities that collectively achieve immune modulation while maintaining tolerance to harmless antigens.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS11723934B2Compositions and methods for the induction of CD8+ T-cells

Publication Date: 2023.08.15 KEIO UNIV

AI summary

Provided herein are compositions and methods for the induction and/or proliferation of CD8+ T-cells. The disclosure also provides methods of treatment of diseases that can be treated by the induction and/or proliferation of CD8+ T-cells.