4-1BB Binding Proteins for Enhanced Immune Response
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Solution Overview
Problem
Current cancer immunotherapy methods, particularly those targeting 4-1BB (CD137), face challenges in effectively enhancing antitumor immune responses and modulating immune cell activities to treat various diseases, including cancers, due to limitations in specific binding proteins and their interactions with immune checkpoints.
Innovation Solution
Development of 4-1BB binding proteins, such as antibodies and antigen-binding fragments, that specifically bind to human 4-1BB, modulating its activities and levels, with high affinity and slow off rates, to enhance immune cell functions and synergize with immune checkpoint inhibitors like PD-1 and PD-L1 mAbs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer immunotherapy methods targeting 4-1BB are used, then antitumor immune responses are enhanced, but the effectiveness is limited due to insufficient binding protein affinity and lack of synergy with checkpoint inhibitors
Solution Approach 1:
The patent develops binding proteins with dual functionality: they specifically bind to 4-1BB on immune cells to enhance activation, and simultaneously synergize with immune checkpoint inhibitors like PD-1 and PD-L1 antibodies. This multi-functional approach allows a single therapeutic strategy to address multiple limitations of current immunotherapy
Solution Approach 2:
The invention achieves superior binding characteristics by optimizing the binding proteins to have high affinity for 4-1BB and slow off rates. These parameter changes in binding kinetics directly improve the reliability and durability of the immunotherapeutic effect
2Reliability
If binding proteins with high affinity and slow off rates are developed, then immune cell functions are enhanced, but the complexity of protein design and production increases
Solution Approach 1:
The patent uses phage display technology as an intermediary method to facilitate the design and selection of binding proteins with optimized affinity and kinetics. This intermediary approach systematically identifies proteins meeting the desired binding parameters without requiring de novo design of complex structures
3Productivity
If binding proteins are used to stimulate immune responses, then anti-tumor effects are enhanced, but the cost and complexity of treatment regimens increase
Solution Approach 1:
The patent combines the binding protein therapy with existing immune checkpoint inhibitor treatments in a unified therapeutic regimen. This merging approach leverages the synergistic interaction between 4-1BB activation and checkpoint inhibition to achieve enhanced anti-tumor effects while utilizing established delivery and administration protocols
Data Source
AI summary
Binding proteins that specifically bind to 4-1BB (CD137) are disclosed. More specifically, antibodies that specifically bind to human 4-1BB are disclosed. These binding proteins may be used to treat or to prevent diseases such as cancers by altering the levels or activities of 4-1BB.