ECDI-Treated Cells Induce Donor-Specific Tolerance
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Solution Overview
Problem
Current methods for inducing donor-specific tolerance in allogeneic islet cell transplantation require life-long immunosuppression, which is toxic to β cells and increases the risk of opportunistic infections, and existing strategies for inducing alloantigen-specific tolerance are either toxic or challenging to implement effectively.
Innovation Solution
Administering ECDI-treated cells before, during, and/or after the administration of donor transplant cells or allografts to induce donor-specific tolerance, utilizing ECDI-treated splenocytes or other cells to promote long-term tolerance without additional immunosuppressive agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If life-long immunosuppression is used to prevent allograft rejection, then graft survival is improved, but β-cell toxicity and risk of opportunistic infections increase
Solution Approach 1:
The patent extracts and eliminates the harmful component (immunosuppression) from the transplantation protocol by inducing donor-specific tolerance through ECDI-treated cells, allowing graft acceptance without systemic immunosuppressive drugs that cause β-cell toxicity and infection risk
Solution Approach 2:
ECDI-treated donor cells serve as an intermediary that mediates tolerance induction by modifying donor antigens to generate regulatory T cells, which then mediate graft acceptance without requiring harmful immunosuppressive agents
2Reliability
If existing strategies for inducing alloantigen-specific tolerance are implemented, then donor-specific tolerance is improved, but toxicity or implementation challenges increase
Solution Approach 1:
The patent changes the chemical parameter of cell treatment by using ECDI (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) to crosslink donor antigens with MHC molecules, creating a modified antigen presentation that specifically induces tolerance without the toxicity of conventional immunosuppressive drugs
Solution Approach 2:
The ECDI-treated donor cells act as a temporary, disposable tolerance-inducing agent that is administered once or a few times to establish long-lasting donor-specific tolerance, eliminating the need for continuous toxic immunosuppression
3Reliability
If existing strategies for inducing alloantigen-specific tolerance are implemented, then donor-specific tolerance is improved, but implementation complexity increases
Solution Approach 1:
The patent performs preliminary action by treating donor cells with ECDI before transplantation, which pre-modifies the donor antigens to induce tolerance in the recipient, simplifying the overall protocol by eliminating the need for complex post-transplantation immunosuppression regimens
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
Achieves long-term or indefinite survival of allogeneic donor cells and allografts without immunosuppression, reducing the risk of rejection and opportunistic infections, and is associated with diminished alloantigen-specific T-cell and antibody responses.
Implementation Method 1
administering ECDI-treated cells before, during, and/or after administration of donor transplant cells or a donor allograft in order to induce tolerance for the cells and/or allograft in a recipient
Data Source
AI summary
The present invention provides methods, systems, and compositions for inducing donor-specific tolerance. In particular, the present invention provides methods of administering ECDI-treated cells before, during, and/or after administration of donor transplant cells or a donor allograft in order to induce tolerance for the cells and/or allograft in a recipient.