TCR Alpha/Beta Depleted Cell Preparations for Immune Reconstitution
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Solution Overview
Problem
Current stem cell transplantation methods face complications such as graft-versus-host disease (GVHD), delayed immune reconstitution, and increased risk of infections due to T cell depletion, which hampers the recovery of the immune system and can lead to relapse of underlying diseases.
Innovation Solution
A cell population is developed with significant depletion of TCR alpha/beta-positive cells, using methods like magnetic cell separation, to reduce GVHD risk and enhance immune reconstitution, while maintaining graft-versus-tumor reactivity, by incorporating TCR gamma/delta-positive cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If T cells are depleted to reduce graft-versus-host disease risk, then GVHD incidence is reduced, but immune reconstitution is delayed and infection risk increases
Solution Approach 1:
The patent extracts and removes TCR alpha/beta-positive cells from the cell preparation using magnetic cell separation, thereby eliminating the primary mediators of GVHD while preserving other beneficial cell populations including TCR gamma/delta-positive cells, NK cells, and stem cells for immune reconstitution
Solution Approach 2:
The patent applies selective depletion targeting only TCR alpha/beta-positive cells while preserving other T cell subsets (TCR gamma/delta-positive cells) and other immune cell populations, creating a non-uniform cell composition that locally eliminates GVHD risk while maintaining immune reconstitution capacity
2Object-affected harmful factors
If TCR alpha/beta-positive cells are depleted, then GVHD is minimized, but the ability to control infections and malignant tissue is reduced
Solution Approach 1:
The patent creates a selectively modified cell population where only TCR alpha/beta-positive cells are removed, preserving TCR gamma/delta-positive cells and NK cells that provide graft-versus-tumor and anti-infection effects, thereby maintaining protective immunity while minimizing GVHD
Solution Approach 2:
The patent converts the potential harm of T cell-mediated GVHD into a benefit by selectively removing only the pathogenic TCR alpha/beta-positive T cells while preserving other immune cell populations that can still provide protective graft-versus-tumor and anti-infection effects
3Object-affected harmful factors
If standard T cell depletion is performed, then GVHD risk is reduced, but graft-versus-tumor effect is compromised
Solution Approach 1:
The patent applies selective depletion that targets only TCR alpha/beta-positive cells while preserving TCR gamma/delta-positive cells and NK cells, creating a differentiated cell population that maintains graft-versus-tumor efficacy through preserved cell subsets while reducing GVHD risk
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 reduces the need for immunosuppressive medications, accelerates immune reconstitution, decreases mortality, and minimizes GVHD, thereby improving patient quality of life and treatment outcomes.
Implementation Method 1
using methods like magnetic cell separation
Data Source
AI summary
The invention relates to a composition, comprising a cell population that can be obtained from bone marrow or from blood, wherein the cell population is depleted of cells that express TCR alpha/beta and cells that express CD19. Such a pharmaceutical composition makes the reconstitution of the immune defense of a person as part of a bone marrow transplant possible. By means of the invention, the time until the immune reconstitution is considerably shortened and the immune responses after treatment are considerably reduced, in particular the occurrence of GVHD. The survival rate of the patients is considerably increased.