Autologous Apoptotic Cells Generate Regulatory T Cells
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Solution Overview
Problem
Current methods for generating regulatory T cells (Tregs) for treating autoimmune diseases and graft-versus-host disease are either toxic, non-natural, or lack control over cell number and function, and existing treatments for these conditions often have limited effectiveness.
Innovation Solution
Ex vivo incubation of leukocytes with autologous apoptotic peripheral blood mononuclear cells (APCs) to generate Tregs, which can be administered to patients to suppress immune responses and treat autoimmune disorders, atopic diseases, and graft-versus-host disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods (IL-10, TGF-β, dexamethasone, vitamin D3) are used to generate Tregs ex vivo, then Treg generation is achieved, but the methods are toxic, non-natural, or lack control over cell number and function
Solution Approach 1:
The patent converts the harmful effect of apoptotic cells (which normally trigger immune responses) into a beneficial effect by using them to induce regulatory T cells. The apoptotic cells, instead of causing inflammation, are used to generate Tregs that suppress immune responses, thereby treating autoimmune diseases and graft-versus-host disease.
Solution Approach 2:
The patent employs autologous apoptotic cells (from the patient's own body) to generate Tregs, allowing the patient's own cells to treat their condition. This self-service approach avoids the need for external toxic substances and uses the patient's biological material to generate therapeutic cells.
2Reliability
If apoptotic cells are infused in vivo to induce Tregs, then immune modulation occurs, but the method lacks control over treatment parameters and cell generation
Solution Approach 1:
The patent performs preliminary action by generating Tregs ex vivo in a controlled laboratory setting before administering them to patients. This allows optimization of treatment parameters, cell number, and function before clinical application, providing control over the therapeutic process that in vivo infusion cannot achieve.
3Reliability
If existing treatments (ECP, immunosuppressive agents) are used for autoimmune diseases and GVHD, then some immune suppression is achieved, but effectiveness is limited and side effects occur
Solution Approach 1:
The patent converts the harmful immune response against self-tissue (characteristic of autoimmune diseases) into a beneficial effect by generating Tregs that specifically suppress pathogenic T cells while preserving self-tolerance. This targeted approach treats the underlying immune dysfunction without the broad suppression and side effects of conventional immunosuppressive agents.
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 method effectively generates Tregs with regulatory activity, providing improved control over treatment protocols and clinical benefits by suppressing immune responses, thereby ameliorating symptoms of various autoimmune and atopic diseases, and reducing graft rejection in transplant recipients.
Implementation Method 1
The recognition of apoptotic-cells ('ACs') occurs via a series of evolutionarily-conserved, AC-associated molecular-pattern receptors ('ACAMPRs') on APCs that recognize and bind corresponding apoptotic-cell-associated molecular patterns ('ACAMPs')
Implementation Method 2
Ex vivo incubation of leukocytes with autologous apoptotic peripheral blood mononuclear cells (APCs) to generate Tregs
Data Source
AI summary
Many cell types in the body can remove apoptotic and cellular debris from tissues; however, the professional phagocyte, or antigen presenting cell (“APC”), has a high capacity to do so. The recognition of apoptotic cells (“ACs”) occurs via a series of evolutionarily-conserved, AC associated molecular-pattern receptors (“ACAMPRs”) on APCs that recognize and bind corresponding apoptotic-cell-associated molecular patterns (“ACAMPs”). These receptors recognize ligands such as phosphotidyl serine and oxidized lipids found on apoptotic cells. Savill et al. (2002); and Gregory et al. (2004).