Canine PD-1 VHH Polypeptides for Immune Checkpoint Blockade
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Solution Overview
Problem
There is a therapeutic need for more potent antibodies that bind canine PD-1 to effectively modulate immune checkpoint activity and treat cancer, as existing antibodies may not adequately inhibit PD-L1 or PD-L2 binding to PD-1 in the tumor microenvironment.
Innovation Solution
Development of canine PD-1-binding polypeptides, specifically comprising VHH domains with defined CDR sequences and a canine Fc region, which can form dimers and exhibit reduced binding to canine Fc receptor components, thereby decreasing PD-L1 binding to PD-1 and modulating immune activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used to bind canine PD-1, then immune checkpoint activity can be modulated, but the binding potency is insufficient to adequately inhibit PD-L1 or PD-L2 binding to PD-1 in the tumor microenvironment
Solution Approach 1:
The patent modifies the antibody structure by replacing the conventional Fab region with VHH domains (single-domain antibody variable regions). This structural parameter change results in enhanced binding affinity and potency to canine PD-1, effectively resolving the insufficiency of existing antibodies in inhibiting PD-L1/PD-L2 binding in the tumor microenvironment
2Object-generated harmful factors
If conventional antibody structures are used, then general immune modulation is achieved, but reduced binding to Fc receptors and complement activation is not obtained
Solution Approach 1:
The patent extracts and removes the conventional Fc region from the antibody structure, retaining only the VHH domain. This extraction eliminates unwanted interactions with Fc receptors and complement activation while preserving the essential PD-1 binding function, thereby reducing harmful side effects while maintaining therapeutic efficacy
3Device complexity
If standard antibody formats are employed, then dual functionality (binding and effector functions) is achieved, but the complexity of the molecular structure increases
Solution Approach 1:
The patent extracts only the essential antigen-binding VHH domain from the complete antibody structure, eliminating the complex Fc region. This simplification reduces molecular complexity while simultaneously improving binding affinity to canine PD-1, as the isolated VHH domain can achieve high affinity without the structural constraints of conventional antibody formats
Data Source
AI summary
Provided herein are VHH-containing polypeptides that bind canine PD-1. In some embodiments, VHH-containing polypeptides that bind and antagonize canine PD-1 are provided. Uses of the VHH-containing polypeptides are also provided.