Chimeric Antigen Receptor with Dual Specificity for MSLN and Tumor Antigens
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Solution Overview
Problem
Current cancer treatments, particularly for pancreas cancer, face challenges in selectively targeting and eliminating cancer cells without harming non-malignant cells, as existing chimeric antigen receptors (CARs) lack specificity for certain tumor-associated antigens.
Innovation Solution
Development of chimeric antigen receptors (CARs) comprising antigen binding domains specific for Mesothelin (MSLN) in combination with one or more antigens such as CLA, CD66c, TSPAN8, and CD318, allowing for enhanced specificity and targeted killing of cancer cells by engineered killer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a single antigen binding domain specific for MSLN is used in CAR, then the CAR can recognize tumor cells, but the specificity for cancer cells is insufficient and may attack non-tumor cells
Solution Approach 1:
The patent combines multiple antigen binding domains (specific for MSLN, CLA, CD66c, TSPAN8, and/or CD318) into a single CAR construct or uses multiple CARs simultaneously. This merging approach ensures that the engineered cells only attack tumor cells that express multiple antigens simultaneously, significantly improving cancer cell specificity while reducing off-target effects on non-tumor cells.
Solution Approach 2:
The patent applies different antigen binding domains with varying specificities to different regions or components of the CAR system. By distributing multiple antigen recognition functions across different binding domains within the same CAR or across multiple CARs, the system achieves localized specificity enhancement at the molecular level, ensuring precise targeting of cancer cells with multiple antigen expressions.
2Reliability
If multiple antigen binding domains are combined in CAR, then the specificity for cancer cells is enhanced, but the device complexity increases
Solution Approach 1:
The patent merges multiple antigen binding domains into unified CAR constructs where several binding specificities are integrated into single molecular entities. This consolidation achieves enhanced cancer cell specificity while managing structural complexity by organizing multiple functions within cohesive CAR architectures rather than requiring entirely separate systems.
Data Source
AI summary
The present invention is directed to a chimeric antigen receptor (CAR), comprising an antigen binding domain specific for MSLN in combination with one or more antigen binding domains specific for an antigen selected from the group consisting of CLA, CD66c, TSPAN8 and CD318; cell populations expressing such CARs and the use of the cell populations for cancer therapy.