Anergic Cell Composition for Persistent Transplant Immune Tolerance
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Solution Overview
Problem
Current immunosuppressive regimens for organ transplantation suppress all immune responses, increasing vulnerability to infections and cancer, while existing methods for inducing antigen-specific T cell anergy are not effective in achieving permanent immune tolerance.
Innovation Solution
A pharmaceutical composition comprising a cell with immune tolerance induced by mixing an inhibitory factor that can inhibit an interaction between CD80/CD86 and CD28, a cell derived from the subject, and an antigen derived from the donor, to induce anergy in T cells, allowing for permanent immune tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If continuous drug immunosuppressive regimen is used to prevent graft rejection, then immune rejection is suppressed, but vulnerability to infections and cancer increases
Solution Approach 1:
The invention segments the immune suppression function into two distinct pathways: (1) continuous non-specific immunosuppression that suppresses all immune responses, and (2) the new anergic cell formulation that provides antigen-specific tolerance. By separating these functions, the patent enables selective suppression of anti-graft immunity while preserving protective immune responses against infections and cancer.
Solution Approach 2:
The anergic T cells serve as an intermediary mechanism between the graft and the recipient's immune system. These engineered cells mediate tolerance by selectively suppressing anti-graft T cell responses through antigen-specific anergy induction, rather than using broad-spectrum immunosuppressive drugs that affect all immune functions.
2Reliability
If antigen-specific T cell anergy is induced to achieve immune tolerance, then graft rejection is prevented, but permanent immune tolerance is not achieved
Solution Approach 1:
The invention applies preliminary action by pre-inducing anergy in T cells before administering them to the recipient. The T cells are exposed to inhibitory factors and donor antigens in vitro to establish anergic state, then these pre-conditioned cells are transferred to the recipient to provide long-lasting tolerance. This preliminary conditioning ensures the cells are already programmed for tolerance before encountering the graft in vivo.
Solution Approach 2:
The invention changes the functional parameters of T cells by modifying their activation state through exposure to inhibitory factors (anti-CD80/CD86 antibodies or CTLA4-Ig). This parameter change transforms normal T cells into anergic T cells that cannot be activated by donor antigens, creating a stable tolerant state that persists long-term in the recipient.
Data Source
AI summary
The present disclosure provides a novel technique relating to immunological tolerance. More specifically, the present inventor found for the first time that, in a technique for inducing immunological tolerance by administering to an organ transplantation patient (a recipient) a cell preparation containing cells in which anergy is induced by an inhibitor inhibiting the interaction between CD80/CD86 and CD28, the immunological tolerance continues even after the disappearance of the cells derived from the cell preparation from the recipient (infectious immunological tolerance). Further, the present inventor proved that such a cell preparation can elicit immunological tolerance against immunological rejection caused by allergy, iPS cells, etc. or cells, tissues or organs derived therefrom.