C4BP Isoform Beta-Chain Deletion for Antigen-Specific Immune Tolerance
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Solution Overview
Problem
Current therapies for autoimmune diseases and immune-related disorders often rely on systemic immune suppression, which can have significant side effects and are not conducive to long-term host survival, highlighting the need for antigen-specific treatments that can block self-reactive immune cell functions while maintaining infection-clearing capabilities.
Innovation Solution
The development of compositions and methods using C4BP isoforms lacking the beta chain, or specific peptides and polynucleotides, to generate tolerogenic dendritic cells that can induce antigen-specific immune tolerance by inhibiting dendritic cell maturation and promoting a tolerogenic phenotype.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If systemic immune suppression is used to treat autoimmune diseases, then immune inflammatory activity is inhibited, but side effects increase and long-term host survival is compromised
Solution Approach 1:
The patent uses C4BP isoform lacking beta chain as an intermediary substance that specifically modulates dendritic cell function. This mediator induces tolerogenic DCs that present autoantigens in a tolerance-inducing manner, thereby blocking self-reactive immune cell functions without requiring broad systemic immune suppression, thus preserving host defense capabilities while treating autoimmune disease
Solution Approach 2:
The invention applies local quality by creating antigen-specific tolerance through tolerogenic dendritic cells that are loaded with specific autoantigens. This approach targets the specific autoimmune response against particular self-antigens rather than suppressing the entire immune system, allowing different regions of the immune response to have different properties - tolerance where needed and immunity where protective
2Object-affected harmful factors
If conventional therapies are used to suppress immune response, then autoimmune disease symptoms are reduced, but the ability to clear infections is compromised
Solution Approach 1:
C4BP isoform lacking beta chain serves as a selective intermediary that modulates only the pathogenic autoimmune arm of the immune response through tolerogenic DC induction, while leaving the protective antimicrobial arm intact. This allows the immune system to distinguish between self-reactive and infection-fighting functions
Solution Approach 2:
The invention segments the immune response into two distinct pathways: a tolerogenic pathway for autoantigen presentation that suppresses autoimmune disease, and a protective pathway for pathogen clearance that remains functional. This segmentation is achieved by using tolerogenic DCs that specifically induce tolerance to self-antigens without affecting immune responses to foreign pathogens
3Duration of action of moving object
If continuous immune suppression therapy is administered, then autoimmune disease is controlled, but long-term host survival is reduced due to numerous side effects
Solution Approach 1:
The C4BP isoform lacking beta chain acts as a safe intermediary that induces long-lasting antigen-specific tolerance through tolerogenic DCs. This mediator produces durable therapeutic effect without the cumulative toxicity and side effects associated with continuous administration of conventional immunosuppressive drugs
Solution Approach 2:
The invention uses tolerogenic dendritic cells as a biological copy or model of the natural tolerance-inducing mechanism that occurs during central tolerance development in the thymus. By replicating this physiological tolerance-induction process ex vivo and administering it to patients, the therapy achieves long-term disease control through restoration of natural immune tolerance mechanisms rather than continuous pharmacological suppression
Data Source
AI summary
The invention relates to methods and reagents for the treatment of immunological diseases. In particular, the invention relates to isoforms of the C4b-binding protein (C4BP) lacking beta chains as well as to fragments and peptides derived thereof and to the uses of these polypeptides for the treatment of immunological diseases such as immunoinflammatory disease, sepsis, an autoimmune disease, transplant rejection, graft-versus-host disease and a hypersensitivity disease. Moreover, the invention relates also the use of factor H for the treatment of immunological diseases. In addition, the invention relates to tolerogenic dendritic cells obtained using the C4BP isoform lacking beta chain, the peptides and fragments thereof and factor H and to the therapeutic uses of said cells.