Lactic Acid Bacteria Surface Display for HPV E7 Mucosal Immunity

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Solution Overview

Problem

Current therapeutic vaccines for HPV-associated cancers, such as cervical intraepithelial neoplasia, only partially regress severe dysplasia to moderate dysplasia and fail to achieve normalcy, necessitating a more effective mucosal immunity-inducing therapeutic oral pharmaceutical composition for HPV infectious diseases and associated tumors.

Innovation Solution

A lactic acid bacterium-containing composition with a wild-type HPV E7 protein or its mutant, fused with an anchor protein, is used to induce mucosal immunity, where the E7 protein is expressed or bound to the bacterium's surface, providing a therapeutic oral pharmaceutical composition for treating HPV infections and associated tumors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapeutic vaccines are used to treat HPV-associated cancers, then severe dysplasia can be regressed to moderate dysplasia, but normalcy cannot be achieved

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidcomplete regression to normalcy
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The invention changes the delivery route parameter from parenteral to oral administration, and modifies the antigen presentation mechanism by expressing E7 proteins on the surface of lactic acid bacteria. This parameter change enables complete regression of severe dysplasia to normalcy by inducing stronger and more comprehensive mucosal immunity compared to existing vaccines.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Lactic acid bacteria serve as an intermediary carrier that presents HPV E7 proteins to the immune system through oral administration. The bacteria act as a natural adjuvant and delivery vehicle, enabling effective antigen presentation and immune induction without requiring injection, thereby achieving complete therapeutic regression.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If prophylactic HPV vaccines are administered, then HPV infection can be prevented, but they can only prevent two types of high-risk HPVs

Engineering Contradiction:
Improveprotection against HPV infectionVSAvoidcoverage of HPV types
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The therapeutic vaccine composition is designed to target multiple high-risk HPV types by incorporating E7 proteins from different HPV strains. The oral lactic acid bacterium-based platform provides universal applicability across multiple HPV types, overcoming the limitation of existing vaccines that only cover two types.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If E7 proteins are continuously increased in expression in epithelial cells, then cervical cancer develops, but existing vaccines cannot eliminate cancer cells

Engineering Contradiction:
Improveelimination of cancer cellsVSAvoidpersistent E7 protein expression
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention converts the harmful persistent E7 protein expression into a beneficial therapeutic target. By using E7 proteins as antigens presented on lactic acid bacteria, the body's immune system is activated to specifically recognize and eliminate cells with persistent E7 expression, turning the cancer-causing mechanism into the basis for cancer cell destruction.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentEP3254693B1Lactic-acid-bacteria-containing composition, oral pharmaceutical composition for treating HPV infection and/or HPV-associated tumors, and mucosal immunity-inducing agent
Publication Date: 2021.04.14 THE UNIV OF TOKYO
  • EP3254693B1 patent drawingFigure 1A~1B
  • EP3254693B1 patent drawingFigure 1C~1D
  • EP3254693B1 patent drawingFigure 2A

AI summary

A lactic acid bacterium-containing composition including a lactic acid bacterium having a human papillomavirus (HPV) E7 protein-derived polypeptide on a surface thereof, wherein the HPV E7 protein-derived polypeptide is included in an amount of 0.03 µg to 1.0 µg per 1 × 108 lactic acid bacteria; a therapeutic oral pharmaceutical composition for at least one of an HPV infectious disease and an HPV-associated tumor which includes the lactic acid bacterium-containing composition; and a mucosal immunity-inducing agent which includes the lactic acid bacterium-containing composition.