Pooled Apoptotic Cell Preparation for GVHD Prevention
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Solution Overview
Problem
Current methods for treating immune disorders, such as graft-versus-host disease (GVHD), autoimmune diseases, and inflammatory conditions, are inadequate due to the limitations of immunosuppressive drugs, which can impair immune reconstitution and have significant side effects, and there is a need for a safe and effective approach to prevent or ameliorate GVHD in allogeneic blood or marrow transplantation.
Innovation Solution
A pooled mononuclear apoptotic cell preparation is developed, comprising mononuclear cells in an early-apoptotic state, obtained from multiple individual blood donors, which are processed to reduce the percentage of non-apoptotic cells and suppress immune activation, allowing for the creation of a pharmaceutical composition that can be used to treat immune disorders without the need for HLA matching.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive drugs are used to treat immune disorders and prevent GVHD, then the incidence of GVHD is reduced, but immune reconstitution is impaired and significant side effects occur
Solution Approach 1:
The patent uses apoptotic cells as an intermediary substance to induce immune tolerance. Instead of directly suppressing the immune system with drugs, apoptotic cells mediate the immune response by interacting with dendritic cells and T-cells to promote regulatory T-cell development and suppress pathogenic immune responses, thereby preventing GVHD without the harmful side effects of conventional immunosuppressive drugs
Solution Approach 2:
The patent changes the state of cells from viable to apoptotic through controlled induction of apoptosis. This parameter change (from living to programmed dying state) transforms the cells into immunomodulatory agents that can induce tolerance without causing the immune suppression and side effects associated with pharmacological immunosuppression
2Reliability
If calcineurin inhibitors are used for GVHD prophylaxis, then acute GVHD is partially inhibited, but T-cell development is impaired and disease relapse risk increases
Solution Approach 1:
Apoptotic cells serve as a natural intermediary that promotes regulatory T-cell development through physiological mechanisms rather than pharmacological inhibition. The apoptotic cells interact with dendritic cells to induce tolerogenic dendritic cells, which in turn promote regulatory T-cell differentiation, providing GVHD protection while preserving beneficial T-cell functions and preventing relapse
Solution Approach 2:
The patent converts the potentially harmful process of apoptosis (cell death) into a beneficial therapeutic mechanism. By inducing controlled apoptosis in donor cells and administering these apoptotic cells to the recipient, the harmful cell death process is transformed into a tolerogenic stimulus that prevents GVHD while maintaining immune function
3Ease of manufacture
If non-matched white blood cells are used to create apoptotic cell pools, then cost-effective immune tolerance induction is achieved, but immune response against apoptotic cells and GVHD from living cells may occur
Solution Approach 1:
The patent applies preliminary action by inducing apoptosis in donor white blood cells before pooling and administration. This preliminary apoptotic transformation eliminates the risk of GVHD from living non-matched cells while preserving the cost-effectiveness of using non-HLA-matched donors. The apoptotic state is established prior to pooling, ensuring safety while maintaining manufacturing efficiency
Solution Approach 2:
The patent extracts the harmful potential of non-matched white blood cells by separating viable cells from apoptotic cells through controlled induction of apoptosis. By taking out the viability element and converting cells to an apoptotic state, the patent eliminates the risk of immune rejection and GVHD while retaining the immunomodulatory benefits of pooled non-matched cells
Data Source
AI summary
Cell preparations comprising a pooled and enriched, mononuclear apoptotic cell population, and a method of preparing this cell preparation are described. The pooled mononuclear apoptotic cell preparation may be obtained from pooled, allogeneic white blood cell fractions that are pooled prior to or following induction of apoptosis. Further, described herein are methods of use of these pooled apoptotic cell preparations for treating an immune disease, an inflammatory disease, an autoimmune disease, or infertility in a subject. For example, a pooled apoptotic cell preparation may be used to treat graft versus host disease (GVHD) in an allogeneic subject.