Macrocyclic Peptides Block PD-1/PD-L1 Interaction
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Solution Overview
Problem
Current therapies for cancer and infectious diseases, such as cancer and chronic infections, face challenges in effectively inhibiting the PD-1/PD-L1 interaction, which leads to immune evasion and exhaustion, limiting the efficacy of treatments.
Innovation Solution
Development of macrocyclic compounds that specifically bind to PD-L1, inhibiting its interaction with PD-1 and CD80, thereby enhancing immune responses and restoring T-cell functionality.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are used to block PD-1/PD-L1 interaction, then immune response is enhanced, but treatment efficacy is limited due to immune evasion and exhaustion
Solution Approach 1:
The patent employs small molecule compounds with molecular weights of 200-500 Da, representing a parameter change from large monoclonal antibodies. These small molecules can penetrate tissues more effectively and reach previously inaccessible immune checkpoints, thereby overcoming immune evasion mechanisms while maintaining or enhancing immune response blockade efficacy
Solution Approach 2:
The patent describes compounds with multiple functional groups including aromatic rings, heterocyclic structures, and various substituents that can simultaneously interact with multiple immune checkpoint proteins. This composite molecular structure enables dual or triple blockade of PD-1/PD-L1, PD-1/PD-L2, and other immune interactions, addressing immune exhaustion through multi-target inhibition
2Reliability
If PD-1/PD-L1 interaction is blocked, then T-cell activity is restored, but the interaction with CD80 remains unaddressed limiting full therapeutic potential
Solution Approach 1:
The patent describes compounds designed with multiple binding interfaces and functional groups that can simultaneously interact with PD-1, PD-L1, PD-L2, and CD80. This multi-functional design allows a single compound to blockade multiple immune inhibitory pathways, providing comprehensive T-cell activity restoration while addressing various interaction mechanisms involved in immune exhaustion
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The macrocyclic compounds effectively block the PD-1/PD-L1 and PD-L1/CD80 interactions, enhancing immune responses, improving treatment outcomes for various diseases, including cancer and infectious diseases by restoring T-cell activity and reducing immune exhaustion.
Implementation Method 1
macrocyclic compounds that bind to PD-L1 and are capable of inhibiting the interaction of PD-L1 with PD-1 and CD80
Data Source
AI summary
The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PDL 1 and PD-L 1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.