Anti-PVRIG Antibodies for PVRIG-PVRL2 Checkpoint Blockade
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current immune checkpoint inhibitors, such as those targeting PD-1 or PD-L1, show variable responses and resistance in cancer treatment, necessitating the development of additional checkpoint inhibitors to enhance immune system capability against cancer.
Innovation Solution
Development of anti-PVRIG antibodies that specifically bind to PVRIG, disrupting the PVRIG-PVRL2 interaction to restore immune cell activation, particularly in cancers with high PVRL2 expression, and can be administered alone or in combination with other immune checkpoint inhibitors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing immune checkpoint inhibitors (PD-1/PD-L1 or CTLA-4 blockers) are used, then some cancer treatment response is achieved, but variable responses and resistance occur between patients
Solution Approach 1:
The patent targets a different immune checkpoint parameter (PVRIG-PVRL2 interaction) rather than the already-saturated PD-1/PD-L1 pathway. By changing the molecular target parameter from PD-1 to PVRIG, the invention addresses patient variability and resistance issues through mechanism diversification rather than incremental improvement of existing therapies
Solution Approach 2:
The invention segments the immune checkpoint inhibition strategy by focusing on a specific receptor-ligand pair (PVRIG and PVRL2) rather than using broad-spectrum checkpoint inhibitors. This segmentation allows for more targeted therapy that can overcome resistance to broader mechanisms while maintaining reliability through specialized action
2Reliability
If additional checkpoint inhibitors are developed to overcome resistance, then treatment effectiveness may improve, but therapy complexity increases
Solution Approach 1:
The anti-PVRIG antibody is designed to serve multiple functions: it blocks the PVRIG-PVRL2 inhibitory interaction, restores immune cell activation, and can be used both as monotherapy and in combination with other checkpoint inhibitors. This multi-functionality allows a single agent to address complexity by providing versatile therapeutic options rather than requiring multiple specialized agents
Solution Approach 2:
The invention introduces anti-PVRIG antibody as an intermediary that specifically disrupts the PVRIG-PVRL2 interaction to restore immune function. This intermediary approach provides a controlled mechanism to overcome resistance without immediately escalating to complex combination therapies, allowing stepwise management of treatment complexity
Data Source
AI summary
Anti-PVRIG antibodies and antigen-binding fragments thereof, are provided, as are related compositions and methods. The antibodies of the disclosure bind to human PVRIG receptor and can block the interaction between the PVRL2 ligand on one cell with PVRIG on an immune cell.