Educated Mononuclear Cell Product for Autoimmune T Cell Modulation

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Solution Overview

Problem

Current treatments for autoimmune diseases like type 1 diabetes are inadequate due to their inability to comprehensively modulate the immune system, leading to persistent autoimmunity and beta-cell destruction.

Innovation Solution

A method involving the use of a bioreactor device to co-culture mononuclear cells from patients with umbilical cord blood stem cells, modulating the T cell compartment to reduce autoreactivity and enhance beta-cell function, thereby improving insulin production and glycemic control.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for autoimmune diseases, then treatment simplicity is maintained, but the ability to modulate the immune system comprehensively is insufficient, leading to persistent autoimmunity

Engineering Contradiction:
Improveimmune system modulation effectivenessVSAvoidtreatment process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The treatment process is segmented into distinct phases: (1) isolation of mononuclear cells from patient blood, (2) co-culture with umbilical cord blood stem cells in a bioreactor, (3) education/modulation of T cells, and (4) reinfusion of educated cells. This segmentation allows each step to be optimized independently while achieving comprehensive immune modulation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Umbilical cord blood stem cells serve as an intermediary mediator that educates and modulates autoreactive T cells. The stem cells interact with patient mononuclear cells in a controlled bioreactor environment, transforming harmful autoreactive T cells into non-autoreactive cells without directly attacking the autoimmune pathology.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If the bioreactor co-culture method is used to educate mononuclear cells, then autoreactivity in T cells is reduced, but the treatment process becomes more complex and time-consuming

Engineering Contradiction:
ImproveT cell autoreactivityVSAvoidtreatment duration
Core Design Contradiction:
Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The bioreactor is pre-prepared with a conditioned environment containing umbilical cord blood stem cells before patient cell introduction. This preliminary setup ensures that when patient mononuclear cells are added, the educational/modulating environment is already optimized, reducing overall treatment time while maintaining effectiveness.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The bioreactor system allows precise control of co-culture parameters including cell ratios, nutrient composition, oxygen levels, and interaction time. By optimizing these parameters, the treatment achieves effective T cell education in reduced timeframes compared to conventional prolonged immunosuppressive therapies.

Inventive Principle:
Principle #35Parameter changes

3Object-generated harmful factors

If current immunosuppressive therapies are applied, then immune response is suppressed, but beta-cell function is not enhanced and insulin production remains inadequate

Engineering Contradiction:
Improveautoimmune attack on beta cellsVSAvoidbeta-cell function and insulin production
Core Design Contradiction:
Object-generated harmful factorsVSReliability

Solution Approach 1:

The treatment converts harmful autoreactive T cells into beneficial non-autoreactive cells through the bioreactor co-culture process. Instead of merely suppressing the immune response, the umbilical cord blood stem cells actively reprogram the T cells, transforming the harmful autoimmune mechanism into a protective, non-autoreactive state that supports beta-cell survival and function.

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

Solution Approach 2:

The therapy combines multiple therapeutic elements: patient's own mononuclear cells, umbilical cord blood stem cells, controlled bioreactor environment, and optimized co-culture conditions. This composite approach simultaneously achieves immune modulation and beta-cell support, addressing both the harmful autoimmune attack and the need for enhanced insulin production.

Inventive Principle:
Principle #40Composite materials

Data Source

PatentEP3504316B1Methods for treating an immune disorder-related disease by reducing autoreactivity in a t cell compartment
Publication Date: 2021.06.23 HACKENSACK UNIVERSTIY MEDICAL CENT
  • EP3504316B1 patent drawingFigure 1
  • EP3504316B1 patent drawingFigure 2
  • EP3504316B1 patent drawingFigure 3A~3B

AI summary

The described invention provides a pharmaceutical composition comprising a therapeutic amount of an educated mononuclear cell product, a process for preparing the educated mononuclear cell product, and a method for treating a disease characterized by lymphocyte autoreactivity. Mononuclear cells from a diseased subject are co-cultured with a viable population of adherent umbilical cord blood stem cells at at least 80% confluence to form an educated mononuclear cell product. A therapeutic amount of the educated mononuclear cell product is returned by infusion intravascularly to the subject. The therapeutic amount is effective to modulate autoreactivity in a T cell compartment of the subject and to reduce symptoms of the disease characterized by lymphocyte autoreactivity.