Apoptotic Mononuclear Cell Preparations for GVHD Reduction
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Solution Overview
Problem
Current methods for treating autoimmune and inflammatory diseases, particularly graft-versus-host disease (GVHD), are inadequate in terms of safety, reliability, and effectiveness, with immunosuppressive drugs causing complications and the optimal approach for GVHD prophylaxis not yet established.
Innovation Solution
Development of a therapeutic composition comprising mononuclear enriched cells in an early apoptotic state, which are administered separately from bone marrow cells during hematopoietic stem-cell transplantation, using anticoagulants like heparin and ACD Formula A to enhance cell yield and stability, thereby reducing GVHD incidence and hepatotoxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive drugs are used to treat or prevent rejection of transplanted organs and tissues, then the immune system is suppressed to allow engraftment, but complications arise including impaired immune reconstitution and increased risk of disease relapse
Solution Approach 1:
The patent uses apoptotic donor mononuclear cells as an intermediary substance to mediate between the donor graft and recipient immune system. These apoptotic cells act as a bridge that induces regulatory T cells and suppresses GVHD without requiring systemic immunosuppression, thereby resolving the contradiction between achieving engraftment and avoiding immune suppression complications
Solution Approach 2:
The patent converts the harmful effect of donor T cells (which cause GVHD) into a beneficial effect by inducing them to undergo apoptosis. The apoptotic donor cells then serve as a therapeutic agent that actively suppresses GVHD and promotes immune tolerance, transforming the original harmful factor into a protective mechanism
2Object-affected harmful factors
If calcineurin inhibitors are used to partially inhibit acute GVHD, then GVHD is reduced, but T-cell development is impaired and the risk of disease relapse increases
Solution Approach 1:
The patent introduces apoptotic donor mononuclear cells as a mediator that selectively suppresses GVHD through induction of regulatory T cells, while leaving normal T-cell development and immune reconstitution unaffected. This intermediary approach achieves GVHD control without the harmful side effects of calcineurin inhibitors on immune function
3Productivity
If donor marrow is infused into the patient's body, then stem cells engraft to restore immune system, but the donor's immune cells recognize patient's tissue as foreign and cause damage
Solution Approach 1:
The patent applies preliminary action by inducing apoptosis in donor mononuclear cells before infusion into the recipient. This pre-treatment modifies the donor cells to prevent them from attacking host tissue, while preserving their ability to restore immune function through engraftment of stem cells and induction of regulatory T cells
Solution Approach 2:
The patent converts the harmful potential of donor immune cells (to cause GVHD) into a beneficial therapeutic effect. By inducing controlled apoptosis in donor mononuclear cells, the patent creates a cell population that actively suppresses GVHD and promotes immune tolerance, transforming the original threat into a protective mechanism
Data Source
AI summary
The present application provides pharmaceutical compositions comprising a population of mononuclear-enriched cells in an early-apoptotic state, methods for the production of said compositions and uses thereof in the treatment of diseases characterized by pathological immune responses. The pharmaceutical compositions may be used in treatment of conditions such as, but not limited to, graft versus host disease (GVHD) and autoimmune diseases including but not limited to inflammatory bowel disease, gout and arthritis.