Anti-TIGIT Antibodies Block Immune Checkpoint for Cancer Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for cancers and viral infections, such as HIV, are limited by the immune checkpoint molecule TIGIT, which suppresses T cell function and contributes to treatment resistance and disease progression.
Innovation Solution
Development of antibodies and antigen-binding fragments specific to the human TIGIT protein, comprising specific heavy and light chain variable region sequences, that inhibit TIGIT's interaction with CD155, enhancing T cell function and immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TIGIT checkpoint molecule is present, then T cell suppression occurs leading to treatment resistance, but blocking TIGIT requires developing new antibodies which increases device complexity
Solution Approach 1:
The patent uses antibodies as intermediary molecules to block the interaction between TIGIT and its ligands (CD155, CD112). The antibodies serve as mediators that prevent the suppressive signaling pathway without requiring direct modification of TIGIT or the ligands, thus improving treatment efficacy while maintaining a manageable level of complexity through a well-established therapeutic approach
Solution Approach 2:
The patent employs parameter changes by modifying antibody structures (heavy and light chain variable regions with specific CDR sequences) to optimize binding affinity and blocking efficiency. By adjusting the molecular parameters of the antibodies, the invention achieves reliable TIGIT blockade while controlling the complexity through rational design rather than trial-and-error approaches
2Productivity
If TIGIT expression is high on T cells, then immune response is suppressed leading to poor clinical outcomes, but targeting TIGIT requires specific antibody sequences that increase manufacturing complexity
Solution Approach 1:
The patent segments the antibody structure into distinct functional components with specific variable region sequences (VH and VL with defined CDRs). This segmentation allows for modular manufacturing where the variable regions can be produced and characterized separately, facilitating easier production while ensuring the segmented components work together to achieve high productivity in immune response activation
Solution Approach 2:
The patent specifies precise parameter changes in the antibody sequences (amino acid sequences in CDR regions) to optimize both binding affinity for TIGIT and manufacturability. By defining specific sequence parameters rather than requiring complex structural features, the invention achieves high immune response activation while improving ease of manufacture through well-defined production specifications
3Reliability
If existing antibodies like Tiragolumab are used, then some TIGIT blocking occurs, but superior efficacy requires developing new antibody sequences that increase development time
Solution Approach 1:
The patent applies preliminary action by pre-defining the optimal CDR sequences and variable region structures through computational design and in silico modeling before experimental validation. This preliminary characterization of the antibody sequences accelerates the development process by reducing the need for extensive trial-and-error optimization, thereby achieving superior efficacy without proportionally increasing development time
Solution Approach 2:
The patent uses copying by identifying and replicating successful binding motifs from known high-affinity antibodies, then optimizing them for TIGIT specificity. By copying and adapting proven structural elements rather than designing entirely de novo, the invention achieves superior efficacy while shortening development time through leveraging existing knowledge
Data Source
AI summary
Provided are anti-TIGIT antibodies and fragments thereof. The antibodies and fragments thereof specifically bind to the TIGIT protein. Methods of using the antibodies or fragments thereof for treating and diagnosing diseases such as cancer and viral infections are also provided.