Anti-TIGIT Antibody Binding Design for Immune Activation
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Solution Overview
Problem
Current therapeutic agents are inadequate in modulating immune responses effectively to treat diseases involving immune suppression, particularly through targeting the TIGIT protein, which suppresses T cell and NK cell activity.
Innovation Solution
Development of antibodies that specifically bind to TIGIT, including specific CDR sequences and constant regions, to enhance immune cell activation and treat cancer or infectious diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic agents are used to modulate immune responses, then treatment of immune suppression diseases is attempted, but they are inadequate in effectively activating immune cells and blocking TIGIT's immunosuppressive functions
Solution Approach 1:
The patent employs parameter changes by modifying the antibody structure to achieve optimal binding affinity and specificity for TIGIT. The antibodies are engineered with specific variable regions that target TIGIT's ligand-binding site, changing the molecular parameters of interaction to effectively block immunosuppressive functions while enhancing immune cell activation
Solution Approach 2:
The anti-TIGIT antibodies serve as intermediary molecules that mediate between the immune system and TIGIT-expressing cells. By binding to TIGIT, these antibodies act as intermediaries to prevent direct ligand-TIGIT interactions, thereby modulating immune responses without requiring direct manipulation of the underlying molecular pathways
2Reliability
If therapeutic agents target TIGIT to enhance immune cell activation, then immune response is improved, but the ability to specifically block TIGIT's interaction with ligands like CD155 is insufficient
Solution Approach 1:
The patent applies local quality by designing antibodies with specific variable regions that target the precise epitope on TIGIT involved in ligand binding. The CDRs are engineered to interact with specific local regions of TIGIT, ensuring high specificity for blocking CD155 and other ligand interactions while maintaining broad immune cell activation capabilities
Solution Approach 2:
The antibody structure is segmented into distinct functional regions: variable regions for specific TIGIT binding, constant regions for effector functions, and engineered CDRs for optimized ligand blocking. This segmentation allows independent optimization of each region's function to achieve both high activation efficacy and specific ligand interaction blocking
Data Source
AI summary
The instant disclosure provides isolated antibodies that specifically bind to TIGIT (e.g., human TIGIT). Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.