Recombinant Immunotoxin With Enzyme-Cleavable Linker
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Solution Overview
Problem
Current cancer treatment options for various tumor types are limited, and there is a need for new therapies that can specifically target cancer cells while sparing healthy tissues.
Innovation Solution
Development of binder-toxin fusion proteins, specifically using anisoplin or its homologues as toxins, conjugated with antibody fragments or mimetics, and a peptide linker that is cleavable by mammalian enzymes but not by plant enzymes, to create targeted cytotoxic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If binder-toxin fusion proteins are developed to target cancer cells, then cancer cell killing efficacy is improved, but treatment options for different tumor types remain limited
Solution Approach 1:
The patent creates a universal binder-toxin fusion protein platform that can be adapted to target multiple different tumor types. The modular design allows the same toxin component (ribotoxin or RNase) to be combined with different binders that recognize various cancer cell surface markers, making the therapy versatile across different tumor types while maintaining high killing efficacy.
Solution Approach 2:
The patent modifies the parameters of existing toxins by using ribotoxins or RNases with specific catalytic activities that can be optimized for different cancer targets. By changing the binder component while keeping the toxin core relatively constant, the system can be tuned to target different tumor types, effectively using parameter changes to achieve versatility.
2Power
If ribotoxin or RNase is used as the toxin component, then catalytic activity and potency are improved, but production in plant systems requires specific enzyme resistance
Solution Approach 1:
The patent introduces a peptide linker as an intermediary component between the binder and the toxin (ribotoxin or RNase). This linker is specifically designed to be resistant to plant proteases, thereby protecting the catalytically potent toxin from degradation during plant-based production while still allowing proper folding and function of the fusion protein.
Solution Approach 2:
The patent applies local quality by making the peptide linker region specifically resistant to plant enzymes while the rest of the fusion protein maintains its natural properties. This localized protection strategy allows the toxin to retain its high catalytic activity and potency without being degraded during plant system production, addressing the manufacturing challenge at a specific location in the protein structure.
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 binder-toxin fusion proteins demonstrate high efficacy in reducing cancer cell viability with minimal impact on healthy cells, offering improved treatment options for cancer by selectively targeting and killing cancer cells.
Implementation Method 1
a peptide linker that is cleavable by mammalian enzymes but not by plant enzymes
Implementation Method 2
Recombinant immunotoxin comprising a ribotoxin or rnase
Data Source
AI summary
The present invention relates to a binder-toxin fusion protein comprising at least one protein binder selected from the group consisting ofan antibodyan antibody fragment or derivative retaining target binding capacity, oran antibody mimetic,a ribotoxin or -protoxin, and optionally, a peptide linker connecting a) and b) and/or a cleavable domain comprised in the protoxin (FIG. 1)