Soluble CD83 Proteins Inhibit Dendritic Cell Maturation
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Solution Overview
Problem
Current treatments for diseases related to dysfunctional cellular immune responses involving dendritic cells, T cells, and B cells are inadequate, as they fail to effectively inhibit the interaction between these immune cells, leading to undesirable immune responses and conditions such as autoimmune diseases and allergies.
Innovation Solution
The use of soluble forms of CD83 proteins, specifically the extracellular domain (hCD83ext), which inhibits the maturation of dendritic cells and reduces their ability to stimulate T cells, thereby disrupting the interaction between dendritic cells and T/B cells, along with antibodies against CD83 proteins for diagnostic purposes and treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for diseases related to dysfunctional cellular immune responses, then the treatment coverage is broad, but the effectiveness in inhibiting interaction between immune cells is insufficient
Solution Approach 1:
The patent uses soluble CD83 molecules as intermediary substances that bind to CD83 on the surface of dendritic cells, blocking the interaction between dendritic cells and T cells. This mediator approach specifically inhibits immune cell interaction while maintaining broad treatment applicability across different immune-mediated diseases.
Solution Approach 2:
The patent modifies the CD83 molecule by creating soluble forms through truncation (removing transmembrane and cytoplasmic domains) and fusion with Fc regions, changing the physical and functional parameters of CD83 to enable therapeutic use while preserving its ability to inhibit immune cell interaction.
2Reliability
If soluble CD83 proteins are used to inhibit dendritic cell maturation, then the immune response is reduced, but the complexity of protein production increases
Solution Approach 1:
The patent extracts only the extracellular domain of CD83 (amino acids 1-125 or 1-144) to create soluble forms, removing the complex transmembrane and cytoplasmic domains. This simplification maintains the therapeutic function of inhibiting dendritic cell maturation while reducing production complexity.
Solution Approach 2:
The patent creates composite molecules by fusing the soluble CD83 extracellular domain with Fc regions of antibodies or other protein domains, combining the immune-modulating properties of CD83 with the stability and ease of production characteristics of Fc proteins.
3Measurement precision
If antibodies against CD83 are used for diagnostic purposes, then the detection precision is improved, but the manufacturing cost increases
Solution Approach 1:
The patent creates simplified copy versions of full CD83 by using only the extracellular domain, which retains the antigen-binding epitopes needed for antibody recognition. This allows diagnostic antibodies to be developed against smaller, easier-to-produce CD83 fragments while maintaining detection precision.
Data Source
AI summary
The present invention provides for the use of soluble forms of CD83 and nucleic acids encoding them for the treatment of diseases caused by the dysfunction or undesired function of a cellular immune response involving dendritic cells, T cells and/or B cells. The invention moreover provides soluble CD83 molecules specifically suited for said purpose, antibodies against said specific soluble CD83 proteins and assay methods and kits comprising said antibodies.