PSGL-1 Antagonists Targeting VISTA Interaction
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Solution Overview
Problem
Current methods lack effective identification and utilization of PSGL-1 antagonists, which are crucial for understanding VISTA-mediated immune inhibition and developing cancer immunotherapies, as the binding partners for VISTA remain unknown, hindering the development of therapeutically effective and safe treatments.
Innovation Solution
The identification of PSGL-1 as a binding partner for VISTA, where antibodies or small molecules that bind to PSGL-1 or VISTA at acidic pH are used to inhibit their interaction, thereby enhancing immune responses against cancer cells by reducing VISTA's immune inhibitory effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the binding partner for VISTA is unknown, then the development of cancer immunotherapies is hindered, but identifying the binding partner requires complex experimental procedures
Solution Approach 1:
The patent uses PSGL-1 as an intermediary molecule to identify and characterize the VISTA binding partner. By introducing PSGL-1 as a mediator in the interaction system, the complex identification problem is simplified through a defined molecular interaction pathway, enabling reliable therapeutic development based on the PSGL-1-VISTA axis
2Object-generated harmful factors
If VISTA-mediated immune inhibition is blocked, then immune responses against cancer cells are enhanced, but the mechanism requires precise pH-dependent binding inhibition
Solution Approach 1:
The patent exploits pH as a critical parameter to control the VISTA-PSGL-1 binding interaction. By utilizing the pH-dependent nature of the binding (functional at acidic pH, inhibited at neutral pH), the therapy achieves selective blocking of VISTA-mediated inhibition under tumor microenvironment conditions without interfering with normal immune function at physiological pH
Data Source
AI summary
Methods of identifying and using PSGL-1 antagonists are provided. Such methods include, but are not limited to, methods of treating cancer. PSGL-1 antagonists include, but are not limited to, antibodies that bind PSGL-1 and antibodies that bind VISTA, wherein the antibodies inhibit PSGL-1 binding to VISTA, e.g., at acidic pH (e.g., pH 6.0), as well as PSGL-1 and VISTA extracellular domain polypeptides.