Mutated IL-34 Polypeptides for Immune Tolerance Modulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing therapies for conditions such as autoimmune diseases, transplantation, cancer, and allergic disorders lack effective agents that can modulate immune responses and improve transplant tolerance or reduce unwanted immune reactions.
Innovation Solution
Development of mutated interleukin-34 (IL-34) polypeptides that act as agonists or antagonists to CSF-1R, PTP-ζ, and CD138 receptors, mimicking or blocking the biological activities of native IL-34 to regulate immune cell functions and induce immune tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies are used for autoimmune diseases and transplantation, then treatment is provided, but effective modulation of immune responses and improvement of transplant tolerance is not achieved
Solution Approach 1:
The patent applies parameter changes by mutating specific amino acid residues in the IL-34 polypeptide sequence to create variants with modified biological activities. These mutations alter the interaction between IL-34 and its receptors (CSF-1R, PTP-ζ, CD138), enabling the development of agonists that enhance transplant tolerance and antagonists that reduce immune rejection, thereby resolving the contradiction between maintaining immune function and preventing rejection.
2Adaptability or versatility
If IL-34 is used to modulate immune responses, then immune cell differentiation and survival are regulated, but unwanted immune reactions may occur
Solution Approach 1:
The patent applies local quality by creating IL-34 variants with specific amino acid mutations that confer different functional properties to different regions of the polypeptide. By modifying specific residues involved in receptor binding or signaling, the invention generates agonists for enhancing immune tolerance and antagonists for suppressing unwanted immune reactions, allowing precise control over immune response modulation.
3Reliability
If mutated IL-34 polypeptides are developed as agonists or antagonists, then therapeutic benefits are achieved, but the complexity of the treatment increases
Solution Approach 1:
The patent resolves this contradiction by making targeted parameter changes through site-specific amino acid mutations in the IL-34 polypeptide. This approach allows the generation of agonists and antagonists with distinct therapeutic profiles while maintaining a relatively simple protein structure based on the native IL-34 sequence, thereby achieving therapeutic efficacy without excessive complexity.
Data Source
AI summary
Interleukin-34 is a cytokine that is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation. The involvement of IL-34 has been shown in areas as diverse as neuronal protection, autoimmune diseases, infection, cancer, and transplantation. Recent work has also demonstrated a new and possible therapeutic role for IL-34 as a Foxp3+ Treg-secreted cytokine mediator of transplant tolerance. New mutated IL-34 polypeptides have been generated, which can be used as agonists or antagonists.