Genetically Engineered Stem Cells for Durable Antibody Production

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Solution Overview

Problem

Current vaccines and immunization strategies struggle to elicit broad and effective immunity against infectious diseases like HIV, influenza, and malaria, as the human immune system is intrinsically incapable of generating lasting immunity against these pathogens, and existing cell therapies face challenges with immune rejection and scalability.

Innovation Solution

The development of genetically engineered stem cells and plasma cells that can differentiate into transplantable, long-lived plasma cells capable of producing broadly neutralizing antibodies, and the use of immune evasion strategies to prevent immune rejection, allowing for the creation of 'off-the-shelf' cellular therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional vaccines are used to elicit immunity, then the immune system is stimulated to produce adaptive immunity, but the immune system is intrinsically incapable of generating broad and lasting immunity against pathogens like HIV, influenza, and malaria

Engineering Contradiction:

Improvelasting immunityVSAvoidbroad immunity against mutable pathogens

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies preliminary action by genetically engineering stem cells in advance to express broadly neutralizing antibodies before transplantation. The engineered stem cells are pre-programmed with the genetic instructions to produce protective antibodies, eliminating the need for the immune system to generate immunity de novo against mutable pathogens like HIV and influenza.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses copying by creating genetically engineered stem cells that replicate and differentiate into plasma cells producing copies of broadly neutralizing antibodies. The engineered stem cells serve as a renewable source that continuously produces antibody copies, providing sustained protection without requiring repeated vaccinations.

Inventive Principle:

Principle #26Copying

2Duration of action of stationary object

If cell therapies are developed to produce therapeutic antibodies, then durable immunity can be achieved, but the cells face immune rejection that limits their clinical application

Engineering Contradiction:

Improvedurable immunityVSAvoidimmune rejection

Core Design Contradiction:

Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful effect of immune rejection into a benefit by using immune evasion strategies. The engineered stem cells are modified to express surface proteins that actively prevent immune recognition and rejection, turning the immune system's potential harm into a protective mechanism that enables long-term persistence of therapeutic cells.

Inventive Principle:

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

Solution Approach 2:

The patent introduces intermediary molecules (immune evasion proteins) that mediate between the engineered stem cells and the host immune system. These intermediary proteins on the cell surface act as shields that prevent direct interaction between immune cells and the engineered stem cells, allowing the therapy to persist without rejection.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If genetically engineered stem cells are used to produce plasma cells, then scalable and cost-effective cellular therapies can be created, but the complexity of genetic manipulation and immune evasion engineering increases

Engineering Contradiction:

Improvescalability of cellular therapyVSAvoidgenetic engineering complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent applies universality by developing a platform technology where a single genetically engineered stem cell line can produce multiple different therapeutic antibodies. The engineered stem cells serve as a universal platform that can be reprogrammed to produce various antibodies against different pathogens, reducing the need to develop separate cell therapies for each indication.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20230313131A1Cells and methods of uses and making the same

Publication Date: 2023.10.05 WASHINGTON UNIV IN SAINT LOUIS

AI summary

Among the various aspects of the present disclosure is the provision of a genetically engineered stem cells, plasma cells, B cells to avoid immune rejection within a host, and methods of making the same and uses thereof.