Acellular Pro-tolerogenic Compositions for Graft Rejection
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Solution Overview
Problem
Current immunosuppressive agents used to prevent acute and chronic rejection in transplantation and autoimmune diseases are plagued by chronic toxicity, and there is a need for alternative methods to modulate immune responsiveness effectively.
Innovation Solution
Development of acellular pro-tolerogenic preparations enriched in specific miRNA species obtained by contacting allogeneic leukocyte populations, one of which has been modified with a low-immunogenic biocompatible polymer to limit pro-inflammatory allo-recognition and promote pro-tolerogenic allo-recognition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive agents are used to prevent rejection, then rejection is minimized or prevented, but chronic toxicity occurs
Solution Approach 1:
The patent extracts and isolates specific miRNA species (particularly miR-155, miR-146a, and miR-125b) from the complex immunosuppressive milieu. By focusing on these specific molecular entities rather than using broad-spectrum immunosuppressive drugs, the invention achieves rejection prevention while minimizing the chronic toxicity associated with conventional agents like cyclosporine and FK506.
Solution Approach 2:
The invention changes the parameter of immunosuppression from non-specific pharmacological inhibition to specific miRNA-mediated gene regulation. By introducing defined miRNA compositions that target specific genes involved in T cell activation and proliferation, the treatment achieves immunosuppression with a different molecular mechanism that avoids the toxic side effects of traditional drugs.
2Productivity
If T cell proliferation is inhibited to prevent rejection, then allo-responsive T cell proliferation is reduced, but immune tolerance is not sufficiently induced
Solution Approach 1:
The patent uses miRNAs as intermediary molecules that mediate between the allogeneic stimulus and the immune response. These miRNAs act as molecular messengers that regulate gene expression in T cells, controlling proliferation while simultaneously inducing tolerance through epigenetic modifications and altered gene expression patterns, rather than simply blocking proliferation.
Solution Approach 2:
The invention employs miRNAs that are introduced before full-blown rejection occurs, acting in a preliminary manner to shape the immune response. The miRNA composition is designed to preemptively regulate gene expression in a way that directs T cells toward tolerance rather than activation, establishing a tolerogenic state before the harmful immune response fully develops.
Data Source
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AI summary
This invention relates to pro-tolerogenic preparations capable of increasing the level of regulatory T cells (Treg) and/or decreasing the level of pro-inflammatory T cells (Th17) to induce anergy or immune tolerance. The pro-tolerogenic preparation is enriched in at least one species of miRNAs and is obtained by contacting two allogeneic leukocyte populations wherein at least one of the two populations is modified with a low-immunogenic biocompatible polymer. Therapeutic uses for preventing or limiting graft rejection and GVHD of such compositions are also provided.