Macrocyclic Peptides Inhibit PD-L1 Immune Evasion
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Solution Overview
Problem
Current therapies for cancer and infectious diseases often fail to effectively inhibit the PD-1/PD-L1 and CD80/PD-L1 protein interactions, leading to immune evasion and suppression, which limits the efficacy of treatments for various diseases, including cancer and chronic infections.
Innovation Solution
Development of novel macrocyclic peptides that specifically inhibit the interaction between PD-L1 and PD-1 or CD80, enhancing T cell functional activity and immune response by blocking these protein interactions, thereby offering a therapeutic approach for cancer and infectious diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to treat cancer and infectious diseases, then treatment is provided, but the PD-1/PD-L1 and CD80/PD-L1 protein interactions are not effectively inhibited, leading to immune evasion and suppression
Solution Approach 1:
The patent employs monoclonal antibodies as intermediary molecules that specifically bind to PD-L1, preventing its interaction with PD-1 and CD80. These antibodies act as mediators that disrupt the harmful protein-protein interactions without directly modifying the target proteins, thereby blocking immune evasion mechanisms while maintaining treatment reliability
Solution Approach 2:
The invention utilizes monoclonal antibodies with specifically engineered binding parameters that target PD-L1 with high affinity and specificity. By changing the binding parameters through antibody design and selection, the therapy effectively inhibits the PD-1/PD-L1 and CD80/PD-L1 interactions, reversing immune suppression and enhancing treatment efficacy
2Reliability
If the PD-1/PD-L1 and CD80/PD-L1 interactions are blocked to enhance immune response, then T cell functional activity is enhanced, but the complexity of the therapeutic approach increases
Solution Approach 1:
The patent employs monoclonal antibodies that can simultaneously block multiple interactions (PD-L1 with both PD-1 and CD80) through a single therapeutic agent. This multi-functional approach enhances immune response efficacy while minimizing the complexity that would arise from using multiple separate therapies for each interaction
Solution Approach 2:
The invention combines the ability to block both PD-1/PD-L1 and CD80/PD-L1 interactions into a single monoclonal antibody therapy. By merging these functions into one therapeutic approach, the patent achieves comprehensive immune response enhancement without the logistical and administrative complexity of multiple separate treatments
Data Source
AI summary
The present disclosure provides novel macrocyclic peptides of formula (I) which inhibit the PD-l/PD-Ll and PD-L1/CD80 protein/ protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.