Autologous Monocyte Antigen Loading for Arteriogenesis

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Solution Overview

Problem

Current treatments for vascular diseases, such as occlusive diseases, face challenges in promoting collateral vessel growth due to risks associated with allogeneic cell transplantation, including immune rejection and transmission of diseases like hepatitis and HIV, and lack of effective methods to induce sufficient inflammation for arteriogenesis.

Innovation Solution

The use of antigen-loaded antigen-presenting cells (APCs), specifically autologous or syngeneic monocytes engineered to present antigens like tetanus toxoid, which are transplanted into immunized subjects to induce a targeted inflammatory response and enhance collateral vessel growth.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If allogeneic monocytes are transplanted to promote arteriogenesis, then collateral vessel growth is strongly promoted, but risks of immune rejection and disease transmission increase

Engineering Contradiction:

Improvecollateral vessel growthVSAvoidimmune rejection and disease transmission

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the immune response by using autologous monocytes that have been ex vivo engineered to present specific antigens. This allows the therapeutic effect to be separated from the risks of allogeneic transplantation, as the cells are genetically identical to the recipient but equipped with targeted antigen presentation capability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces antigen-loaded autologous monocytes as an intermediary between the recipient's immune system and the ischemic tissue. These engineered cells act as mediators that present antigens to the immune system, triggering a controlled inflammatory response that promotes arteriogenesis without the hazards of allogeneic cell transplantation.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If autologous monocytes are transplanted to avoid immune rejection, then safety is improved, but inflammatory response and arteriogenesis are insufficient

Engineering Contradiction:

Improveimmune rejection and disease transmissionVSAvoidinflammatory response and collateral growth

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The invention changes the functional parameters of autologous monocytes by ex vivo engineering to express specific antigens on their surface. This parameter modification allows the cells to activate the immune system and trigger inflammation while maintaining the safety profile of autologous cells.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies preliminary action by pre-loading autologous monocytes with antigens before transplantation. This ex vivo antigen loading prepares the cells to immediately trigger an immune response upon transplantation, overcoming the insufficient inflammatory response of unmodified autologous cells.

Inventive Principle:

Principle #10Preliminary action

3Adaptability or versatility

If immune suppression is used to enable allogeneic cell transplantation, then cell transplantation is feasible, but transmission of hepatitis and HIV risks remain

Engineering Contradiction:

Improvecell transplantation feasibilityVSAvoiddisease transmission

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The invention converts the potential harm of using allogeneic cells into benefit by using autologous cells instead. The same mechanism of immune activation is achieved, but without the risk of disease transmission, as the cells are derived from the recipient's own immune system.

Inventive Principle:

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

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 augments collateral vessel growth by triggering a natural immune response, providing a safer and more effective method than traditional treatments, with the added benefit of long-lasting immunity and reduced need for immune system boosting, allowing for repetitive cell transplantation.

Implementation Method 1

APCs, preferably monocytes, in particular autologous or syngeneic monocytes, are engineered ex vivo, hereinafter also termed in vitro, to present an antigen, preferably tetanus toxoid (TT) antigen

Methodology Applied

Scientific EffectAntigen presentation:

Data Source

PatentEP2846817B1Transplantation of modified monocytes

Publication Date: 2018.10.17 OTTO VON GUERICKE UNIV MAGDEBURG

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AI summary

The present invention relates to antigen-loaded antigen-presenting cells (APC) for use in a therapeutic method for augmenting collateral vessel growth in a subject in need thereof, methods to use said antigen-loaded antigen-presenting cells and pharmaceutical compositions comprising antigen-loaded antigen-presenting cells.