Anti-mesothelin CAR for Solid Cancer Fibrous Tissue Barrier
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Solution Overview
Problem
Current immuno-anticancer agents, such as immune checkpoint inhibitors and CAR-T cell therapies, are less effective for solid cancers due to interference from fibrous tissue, making it difficult for drug delivery, and there is a need for a specific antibody that targets mesothelin, a protein overexpressed in various solid cancers.
Innovation Solution
Development of an anti-mesothelin chimeric antigen receptor (CAR) that includes an antigen-binding domain, a hinge domain, a transmembrane domain, and an intracellular signaling domain, specifically binding to mesothelin, and a method for producing the anti-mesothelin antibody or its antigen-binding fragment, including nucleic acid encoding and vectors for host cell transformation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immuno-anticancer agents (checkpoint inhibitors, CAR-T) are used, then they show effectiveness in certain cancers, but they fail to respond significantly in solid cancers due to fibrous tissue interference
Solution Approach 1:
The patent develops a novel antibody (MSLN3) with optimized binding parameters to mesothelin, achieving high affinity (KD value of 1.31 nM) and specific recognition of mesothelin-overexpressing solid cancer cells. This parameter optimization enables the antibody to effectively target cancer cells despite the presence of fibrous tissue barriers.
2Measurement precision
If a specific anti-mesothelin antibody is developed, then it can target mesothelin-overexpressing solid cancer cells, but it requires extensive research and development to achieve high specificity and affinity
Solution Approach 1:
The patent employs phage display technology to create and screen a library of antibody variants, effectively copying and testing numerous antibody sequences to identify those with high specificity and affinity for mesothelin. This approach systematically identifies optimal antibody candidates without requiring de novo design of each antibody structure.
3Stability of the object's composition
If fibrous tissue surrounds the tumor, then it protects the tumor microenvironment, but it interferes with immunotherapeutic response and makes drug delivery difficult
Solution Approach 1:
The patent extracts and targets the specific antigen mesothelin that is overexpressed on the surface of solid cancer cells, using a highly specific antibody to bind directly to the cancer cells. This approach bypasses the fibrous tissue barrier by targeting surface-expressed antigens rather than requiring deep penetration into the tumor microenvironment.
Data Source
AI summary
Provided is an anti-mesothelin chimeric antigen receptor that specifically binds to mesothelin. The anti-mesothelin chimeric antigen receptor according to an aspect exhibits a specific binding ability for mesothelin, and thus, may be useful for preventing or treating cancer in which mesothelin is overexpressed.