Multivalent CD20-Binding Molecule with Shiga Toxin for Rapid Cellular Internalization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for therapeutic agents that can efficiently target and internalize CD20-expressing cells, as CD20 antigens on the cell surface do not readily internalize upon binding, making it challenging for existing therapies to deliver toxins effectively to these cells.
Innovation Solution
Multivalent CD20-binding molecules comprising multiple CD20-binding regions and Shiga toxin A Subunit effector polypeptides are engineered to promote rapid cellular internalization of CD20, allowing for the selective delivery of cytotoxic agents into CD20-expressing cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibody-based therapies are used to target CD20 antigens, then CD20-expressing cells can be bound by therapeutic agents, but the therapeutic agents cannot efficiently internalize into the cells because CD20 does not readily internalize upon binding
Solution Approach 1:
The therapeutic agent is divided into multiple functional segments: CD20-binding regions (such as antibody fragments) and toxin effector regions (such as Shiga toxin A subunit). This segmentation allows the binding portion to specifically attach to CD20 while the effector portion is positioned to be delivered into the cell, resolving the contradiction between specific binding and internalization efficiency
Solution Approach 2:
The patent creates composite therapeutic molecules that combine CD20-binding domains with toxin effector domains into a single chimeric structure. This composite design enables the molecule to simultaneously achieve high-affinity binding to CD20 and efficient internalization into the target cell, as the toxin portion is naturally equipped to traverse cellular membranes
2Object-affected harmful factors
If toxin effector regions are delivered into CD20-expressing cells, then selective cytotoxicity can be achieved, but the toxin must first overcome the barrier of CD20's resistance to internalization
Solution Approach 1:
The CD20-binding molecule serves as an intermediary that bridges the extracellular toxin and the intracellular target. The molecule's structure includes both the CD20-binding component that attaches to the cell surface and the toxin effector component that is delivered into the cell, thereby mediating the transfer of cytotoxic activity across the cellular barrier without requiring complex external delivery systems
Solution Approach 2:
The patent modifies molecular parameters by engineering chimeric proteins with specific structural configurations that optimize both binding affinity and internalization efficiency. By adjusting the molecular architecture, linkage types, and domain compositions, the therapeutic agent achieves the dual functionality of specific binding and efficient toxin delivery, reducing the need for additional complex delivery mechanisms
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
These molecules enable efficient cellular internalization and cytotoxicity of CD20-expressing cells, including malignant B-cells, by delivering Shiga toxin effector polypeptides to the cytosol, effectively killing targeted cells while minimizing impact on non-target cells.
Implementation Method 1
promote rapid cellular internalization of CD20, allowing for the selective delivery of cytotoxic agents into CD20-expressing cells
Implementation Method 2
delivering Shiga toxin effector polypeptides to the cytosol, effectively killing targeted cells
Data Source
AI summary
Provided herein are multivalent CD20-binding molecules, and compositions thereof, for use in selective killing of specific cell types and/or as therapeutics for the treatment of a variety of diseases, including cancer, tumors, and immune disorders. Certain multivalent CD20-binding molecules can be used to deliver agents into CD20-expressing cells, collecting diagnostic information, and/or monitoring the treatment of diseases, such as cancers, tumors, and immune disorders.