TIGIT Antibodies Binding Affinity and Combination Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current TIGIT-targeting agents have limited therapeutic utility as monotherapies in treating immune-related diseases, such as cancer and infections, due to their inability to effectively modulate TIGIT function and overcome immune checkpoint inhibition.
Innovation Solution
Development of novel antibodies and antigen-binding fragments that specifically bind to TIGIT, reducing or blocking its interaction with CD155, offering improved binding affinity, cross-reactivity, and antibody-dependent cell-mediated cytotoxicity, which can be used alone or in combination therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current TIGIT-targeting agents are used as monotherapies, then treatment simplicity is maintained, but therapeutic utility is limited due to inability to effectively modulate TIGIT function
Solution Approach 1:
The patent combines multiple TIGIT-targeting antibodies with different mechanisms of action into a combination therapy regimen. This merging of therapeutic agents allows simultaneous blockade of TIGIT-CD155 interaction and enhancement of antibody-dependent cell-mediated cytotoxicity, thereby achieving effective TIGIT function modulation that neither agent could achieve alone as a monotherapy.
2Reliability
If novel antibodies with improved binding affinity are developed, then TIGIT binding effectiveness is enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent utilizes affinity maturation techniques to optimize antibody sequences, making precise parameter changes to the variable regions of the antibodies. This allows achievement of improved binding affinity through targeted sequence optimization rather than complete redesign, thereby enhancing TIGIT binding effectiveness while controlling manufacturing complexity through focused modifications.
3Reliability
If combination therapies are implemented, then therapeutic efficacy is improved, but treatment complexity increases
Solution Approach 1:
The patent designs the antibody combination regimen where each antibody contributes multiple functions: blocking TIGIT-CD155 interaction to prevent inhibitory signaling, and serving as an effector antibody to recruit immune cells for ADCC. This multi-functionality of the therapeutic agents improves overall therapeutic efficacy while reducing the need for additional separate agents, thereby managing treatment complexity.
Data Source
AI summary
Antibodies and antigen-binding fragments that bind to TIGIT are disclosed. The disclosure further relates to methods and compositions for use in treating an immune-related disease (e.g., a cancer or an infection or infectious disease) by administering a composition disclosed herein.