Mesothelin Binding Proteins for Cancer Therapy
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Solution Overview
Problem
Current therapies for mesothelin-expressing cancers, such as ovarian, pancreatic, lung, and triple-negative breast cancers, have limited efficacy and new treatments are needed to improve outcomes for patients with these aggressive tumor types.
Innovation Solution
Development of a single domain mesothelin binding protein that specifically binds to mesothelin, utilizing a VHH domain derived from a non-human source, such as llama, which can selectively target and mediate T cell killing of tumor cells expressing mesothelin, potentially used in combination with other agents for enhanced therapeutic effect.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used for mesothelin-expressing cancers, then treatment is available, but efficacy is limited
Solution Approach 1:
The patent introduces a single domain mesothelin binding protein as an intermediary that specifically binds to mesothelin on tumor cells. This binding protein serves as a mediator that directs T cells to the target tumor cells, enabling selective immune-mediated killing. The binding protein acts as a bridge between the immune system (T cells) and the tumor cells expressing mesothelin, thereby improving therapeutic efficacy while maintaining specificity.
2Measurement precision
If a single domain binding protein is used, then specificity to mesothelin is improved, but device complexity is reduced
Solution Approach 1:
The patent extracts only the essential binding domain (single domain/VHH domain) from a complete antibody structure. This single domain protein retains the ability to specifically bind to mesothelin while eliminating the complexity of full antibody structures. The extracted single domain maintains high binding specificity for mesothelin while being structurally simpler and more manageable for therapeutic application.
3Strength
If T cell killing is mediated, then tumor cell destruction is enhanced, but immune response complexity increases
Solution Approach 1:
The single domain mesothelin binding protein serves as an intermediary that simplifies the immune mechanism by providing a direct binding interface between T cells and mesothelin-expressing tumor cells. This mediator approach enhances tumor cell killing capability while managing immune response complexity through a focused, specific binding interaction rather than requiring complex immune system coordination.
Data Source
AI summary
Disclosed herein are MSLN binding proteins with improved binding affinities and improved ability to mediate T cell dependent killing of cancer cells expressing mesothelin. Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of using such formulations are further provided.