Modified CH2 Domain Binding EphA2 Receptor
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current EphA2 receptor-targeting therapies face challenges due to the large size of antibodies and their conjugates, which hinder effective delivery and binding to cancer cells, and small antibody-like molecules have short half-lives, limiting their therapeutic efficacy.
Innovation Solution
A modified isolated immunoglobulin CH2 domain with specific amino acid substitutions, additions, or deletions is developed to bind to the EphA2 receptor, potentially combined with a toxin for targeted cancer therapy, enhancing binding affinity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If full-length antibodies are used to target EphA2 receptor, then binding specificity and therapeutic activity are improved, but molecular size increases causing poor delivery and reduced tumor penetration
Solution Approach 1:
The patent segments the full-length antibody into functional domains (CH2 domain binding to EphA2 receptor, Fc domain providing stability and half-life), allowing the binding function to be separated from the structural bulk, thereby achieving small size with maintained specificity
Solution Approach 2:
The patent extracts only the essential binding capability from the full-length antibody and incorporates it into a minimal CH2 domain framework, removing unnecessary structural elements while retaining the core function of EphA2 receptor binding
2Volume of moving object
If small antibody-like molecules (scFVs) are used to reduce size, then delivery to tumor is improved, but half-life becomes very short reducing therapeutic efficacy
Solution Approach 1:
The patent merges the small CH2 domain (providing size reduction) with the Fc domain (providing extended half-life through FcRn interaction), creating a hybrid molecule that simultaneously achieves both small size and prolonged circulation time
Solution Approach 2:
The patent creates a composite protein structure combining two different functional domains (CH2 and Fc) with complementary properties, where the CH2 domain provides target binding and size reduction while the Fc domain provides stability and extended half-life
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 modified CH2 domain effectively targets and binds to EphA2 receptors, potentially leading to improved tumor uptake and selective killing of cancer cells, with enhanced stability and prolonged half-life, thereby addressing the limitations of existing therapies.
Implementation Method 1
A modified isolated immunoglobulin CH2 domain that specifically binds to an EphA2 receptor
Data Source
AI summary
The present disclosure is directed to a modified isolated immunoglobulin CH2 domain that specifically binds to an extracellular region of an EphA2 receptor, wherein the amino acid sequence of the modified immunoglobulin CH2 domain includes at least one amino acid substitution, addition or deletion in comparison to a wild type immunoglobulin CH2 domain amino acid sequence, wherein the wild type immunoglobulin CH2 domain amino acid sequence includes SEQ ID NO:1 or SEQ ID NO:2. Heterologous immunoconjugates including fusion proteins and pharmaceutical compositions including the modified isolated immunoglobulin CH2 domain are also disclosed. In addition, methods of treating a disease associated with EphA2 overexpression and methods for killing a target cell expressing EphA2 receptors using the modified isolated immunoglobulin CH2 domain are provided.