Anti-PVRIG Antibodies for Selective Immune Checkpoint Blockade
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Solution Overview
Problem
Current therapeutic approaches targeting costimulatory molecules for treating autoimmune diseases, inflammatory diseases, and cancer are limited by their impact on the immune system's ability to defend against pathogens, and there is a need for additional agonists and antagonists of immune checkpoint pathways to overcome immune tolerance and stimulate anti-tumor responses.
Innovation Solution
Development of anti-PVRIG antibodies or fragments that inhibit the binding association of PVRIG polypeptide with PVRL2, utilizing screening methods involving surface interactions, cell-based assays, and FRET signals to identify inhibitors capable of modulating costimulatory signals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If blocking costimulation using monoclonal antibodies or soluble fusion proteins is used to treat autoimmune diseases and cancer, then immune responses are modulated and pathological conditions are treated, but the immune system's ability to defend against pathogens is compromised
Solution Approach 1:
The patent applies local quality by developing antibodies with different specificities against distinct costimulatory molecules (CD28, ICOS, PD-1, CTLA-4, OX40). Each antibody targets a specific molecular pathway, allowing selective modulation of immune responses. This enables treatment of specific pathological conditions while preserving other immune functions through compartmentalized targeting of different costimulatory pathways.
2Reliability
If induction of co-inhibition using soluble fusion protein of inhibitory ligand is used to treat autoimmune diseases, then uncontrolled immune responses are turned off, but the distinction between auto-reactive T cells and pathogen-defending T cells is lost
Solution Approach 1:
The patent segments the costimulatory pathway into multiple distinct molecular targets (CD28, ICOS, PD-1, CTLA-4, OX40), each with specific roles in T cell activation and regulation. By targeting specific segments of this pathway with selective antibodies, the invention can modulate immune responses with greater precision, potentially preserving the ability to distinguish between auto-reactive and pathogen-defending T cells through pathway-specific intervention.
Data Source
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AI summary
The present invention is directed to PVRIG polypeptides and their uses.