Tim-3-Ig Fusion Protein Blocking Signaling Pathway
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies lack effective blocking agents for the Tim-3 signaling pathway, which is implicated in immune dysfunction and autoimmune diseases, hindering the treatment and diagnosis of conditions like systemic lupus erythematosus, asthma, inflammatory bowel disease, and type I diabetes mellitus.
Innovation Solution
A Tim-3-Ig fusion protein is developed, combining a Tim-3 fragment with an IgG fragment, enhancing biological activity and specificity, to competitively block the Tim-3 and Gal-9 interaction, thereby modulating immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a Tim-3 blocking agent is developed to treat immune dysfunction and autoimmune diseases, then immune response modulation is improved, but the lack of effective blocking agents with good effects remains a problem
Solution Approach 1:
The patent uses an IgG Fc fragment as an intermediary to create a fusion protein that blocks Tim-3 signaling. The IgG Fc portion serves as a mediator that can bind to Tim-3 and prevent its interaction with Gal-9, thereby blocking the immunosuppressive signal pathway while leveraging the well-established production capabilities of IgG-based therapeutics
Solution Approach 2:
The invention creates a composite protein structure by fusing Tim-3 extracellular domain with IgG Fc fragment. This composite fusion protein combines the specificity of Tim-3 binding with the enhanced stability, solubility, and manufacturability of IgG-based molecules, resulting in a therapeutic agent with improved blocking efficacy and production feasibility
2Reliability
If Tim-3 and Gal-9 combination is blocked to enhance T-effector cell activities, then immune function recovery is improved, but the molecular weight increase may influence correct combination between Tim-3 and its ligand
Solution Approach 1:
The patent segments the Tim-3 protein by using only its extracellular domain (amino acids 1-209) rather than the full-length protein. This segmentation maintains the ligand-binding capability while removing potential interfering regions, and the segmented Tim-3 is then fused to IgG Fc to create a functional blocking agent with appropriate molecular characteristics
Solution Approach 2:
The fusion protein is designed with specific local quality characteristics by positioning the Tim-3 extracellular domain at the N-terminus and the IgG Fc fragment at the C-terminus, connected by a linker peptide. This local arrangement ensures that the Tim-3 binding region maintains its structural integrity and binding capability while the IgG Fc portion provides the necessary structural support and stability
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The Tim-3-Ig fusion protein effectively blocks the Tim-3 signaling pathway, promoting immunological balance, enhancing Th1 effector cell functions, and inhibiting autoimmune disease progression, as demonstrated by its ability to up-regulate cytokine expression and inhibit tumor growth in preclinical models.
Implementation Method 1
to competitively block the Tim-3 and Gal-9 interaction, thereby modulating immune responses
Data Source
AI summary
The present invention provides a human Tim-3-Ig fusion protein which can block Tim-3 signal pathway, and said Ig fusion protein comprises Tim-3 protein, human Ig fragment, and the linking sequence therebetween. In the present invention, a human Tim-3-Ig gene is obtained by an artificial synthesis process; an expression vector containing the Tim-3-Ig gene is constructed; and the prepared Ig fusion protein is tested in an expression verification experiment, a binding activity experiment, a blocking activity experiment in different cell lines, and in vivo experiments in mice. The human Tim-3-Ig fusion protein prepared in the present invention can be used to treat immunological diseases caused by high expression of Tim-3.