Depleting TCRab and CD45RA Cells for Immune Reconstitution
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current stem cell transplantation methods face complications such as Graft-versus-host-disease, failure of engraftment, and incomplete immune reconstitution due to the presence of TCR alpha/beta and CD45RA positive cells, which can be addressed by developing a method to deplete these cells while retaining memory T cells and other immune cells for enhanced immune reconstitution and infection control.
Innovation Solution
A method involving the depletion of TCR alpha/beta and CD45RA positive cells from bone marrow or blood samples using magnetic cell separation techniques, dividing the sample into fractions, labeling cells with specific markers, and removing labeled cells to achieve a cell population suitable for hematopoietic reconstitution and immune system reconstruction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If TCR alpha/beta and CD45RA positive cells are depleted from the cell composition, then GvHD risk and alloreactivity are reduced, but immune reconstitution capability and infection control are worsened
Solution Approach 1:
The depletion process is segmented into two distinct stages: first depleting TCR alpha/beta positive cells to reduce alloreactivity, then depleting CD45RA positive cells to further reduce GvHD risk. This segmented approach allows selective removal of harmful cells while preserving beneficial memory T cells that are TCR alpha/beta positive but CD45RA negative
Solution Approach 2:
The invention applies different depletion strategies to different cell populations based on their specific characteristics. TCR alpha/beta positive cells are depleted to remove alloreactive potential, while CD45RA positive naive T cells are selectively removed. Memory T cells (TCR alpha/beta positive, CD45RA negative) are preserved to maintain immune reconstitution capability, achieving local quality differentiation in the cell composition
2Object-affected harmful factors
If TCR alpha/beta positive cells are depleted to reduce alloreactivity, then GvHD prevention is improved, but pathogen-specific T cell response is worsened
Solution Approach 1:
The invention extracts only the harmful subset of TCR alpha/beta positive cells (those that are CD45RA positive and therefore naive/alloreactive) while leaving the beneficial subset (TCR alpha/beta positive, CD45RA negative memory T cells) intact. This selective extraction resolves the contradiction by removing alloreactivity without sacrificing pathogen-specific response capability
Solution Approach 2:
The invention changes the depletion parameter from simply depleting all TCR alpha/beta positive cells to depleting TCR alpha/beta positive cells that are also CD45RA positive. This parameter modification allows selective removal of naive T cells while preserving memory T cells, thereby maintaining pathogen-specific responses while reducing alloreactivity
3Object-affected harmful factors
If CD45RA positive cells are depleted to reduce naive T cell alloreactivity, then GvHD prophylaxis is improved, but overall T cell diversity is worsened
Solution Approach 1:
Instead of depleting all T cells or using broad depletion strategies that reduce diversity, the invention inverts the approach by selectively depleting only CD45RA positive naive T cells while preserving CD45RA negative memory T cells. This inverted selectivity maintains T cell diversity by preserving the beneficial memory compartment while removing only the harmful naive compartment
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
The method effectively reduces TCR alpha/beta and CD45RA positive cells by multiple logarithmic steps, retaining memory T cells and other immune cells, enhancing immune reconstitution and infection control, thereby improving the safety and efficacy of stem cell transplantation and adoptive cellular therapy.
Implementation Method 1
labeling the cells of the first fraction with a first marker against TCR alpha/beta, c) labeling the cells of the second fraction with a second marker against CD45RA, d) removing the labeled cells from the first and second fraction
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The invention is directed to a method for the preparation of a cell population from a sample originating from bone marrow or blood, comprising the steps a) dividing the sample into a first fraction containing 50 to 99 % of the cells of the sample and a second fraction containing 50 to 1 % of the cells of the sample, b) labeling the cells of the first fraction with a first marker against TCR alpha/beta, c) labeling the cells of the second fraction with a second marker against CD45RA, d) removing the labeled cells from the first and second fraction and combining the remaining cells to a cell population. Furthermore, the invention is directed to a cell composition and the use of the cell composition