Donor-Derived CD34+ and CD3+ Cells Establish Mixed Chimerism

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Solution Overview

Problem

Organ transplant recipients often face graft rejection due to their immune system identifying the transplanted organ as foreign, necessitating lifelong immunosuppressive therapy, which comes with risks and side effects, and many do not establish mixed chimerism due to lack of access to appropriate regimens at the time of transplantation.

Innovation Solution

The use of cellular products containing CD34+ and CD3+ cells derived from post-surgical apheresis products from a solid organ donor, which can be administered at any time post-transplantation to establish mixed chimerism, allowing for the discontinuation of immunosuppressive therapy and preventing graft-versus-host disease.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immunosuppressive therapy is administered to prevent graft rejection, then graft acceptance is improved, but the risk of infection, cancer, hypertension, and liver damage increases

Engineering Contradiction:
Improvegraft acceptanceVSAvoidside effects of immunosuppression
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the essential function of immune suppression (preventing graft rejection) and separates it from the harmful effects by introducing donor-derived immune cells that specifically tolerate the graft while leaving the rest of the recipient's immune system functional. This selective approach removes the need for broad immunosuppression.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses donor-derived immune cells as an intermediary between the recipient's immune system and the transplanted graft. These intermediary cells induce tolerance to the graft without requiring systemic immunosuppression, thereby mediating acceptance while avoiding the harmful side effects of conventional therapy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If immunosuppressive therapy is administered to prevent graft rejection, then graft acceptance is improved, but the risk of infection, cancer, hypertension, and liver damage increases

Engineering Contradiction:
Improvegraft acceptanceVSAvoidincreased risk of infection and cancer
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts the essential function of immune suppression (preventing graft rejection) and separates it from the harmful effects by introducing donor-derived immune cells that specifically tolerate the graft while leaving the rest of the recipient's immune system functional. This selective approach removes the need for broad immunosuppression.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses donor-derived immune cells as an intermediary between the recipient's immune system and the transplanted graft. These intermediary cells induce tolerance to the graft without requiring systemic immunosuppression, thereby mediating acceptance while avoiding the harmful side effects of conventional therapy.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If mixed chimerism is established using donor-derived hematopoietic cellular compositions, then graft tolerance is improved and immunosuppression can be discontinued, but the complexity of the transplantation regimen increases

Engineering Contradiction:
Improvegraft toleranceVSAvoidcomplexity of transplantation regimen
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by administering donor-derived immune cells at the time of transplantation or shortly thereafter, establishing mixed chimerism before the recipient's immune system can reject the graft. This proactive approach simplifies the overall regimen by preventing rejection rather than requiring lifelong suppression.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the parameter of immune system composition by introducing donor-derived cells to create mixed chimerism. This fundamental change in the immune system's cellular makeup enables graft tolerance without the need for continuous immunosuppressive therapy.

Inventive Principle:
Principle #35Parameter changes

4Object-affected harmful factors

If mixed chimerism is established to allow discontinuation of immunosuppressive therapy, then the risks of immunosuppression are reduced, but the difficulty of establishing mixed chimerism increases

Engineering Contradiction:
Improverisks of immunosuppressionVSAvoiddifficulty of establishing mixed chimerism
Core Design Contradiction:
Object-affected harmful factorsVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies preliminary action by administering donor-derived immune cells at the time of transplantation or shortly thereafter, establishing mixed chimerism before the recipient's immune system can reject the graft. This proactive approach simplifies the overall regimen by preventing rejection rather than requiring lifelong suppression.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the parameter of immune system composition by introducing donor-derived cells to create mixed chimerism. This fundamental change in the immune system's cellular makeup enables graft tolerance without the need for continuous immunosuppressive therapy.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS11819521B2Cellular compositions derived from prior organ donors and methods of manufacture and use thereof
Publication Date: 2023.11.21 MEDEOR THERAPEUTICS INC

AI summary

The invention provides methods of making and using compositions for establishing mixed chimerism in a subject that include CD34+ cells and CD3+ cells derived from an apheresis product obtained from a subject that has previously donated a solid organ.