Monoclonal Antibodies Blocking PVR-TIGIT Interaction for Cancer Immunotherapy
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Solution Overview
Problem
Current cancer therapies face challenges in effectively inhibiting the binding of poliovirus receptor (PVR) to TIGIT, which hinders immune cell activation and tumor targeting, necessitating the development of more specific and potent agents to enhance immune response against cancer cells.
Innovation Solution
Development of high-affinity monoclonal antibodies and fragments that specifically bind to PVR, preventing its interaction with TIGIT, thereby restoring the activity of T and NK cells and enhancing immune cell activation, with the potential for use in combination with other anti-cancer agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer therapies are used to inhibit PVR-TIGIT binding, then immune cell activation is hindered, but developing more specific and potent agents increases therapy complexity and cost
Solution Approach 1:
The patent extracts and isolates the specific PVR-TIGIT interaction as the target for inhibition. By identifying PVR as a distinct tumor-associated antigen and developing antibodies that specifically block its interaction with TIGIT on immune cells, the therapy targets only the problematic interaction without affecting other immune pathways, thereby simplifying the therapeutic approach while maintaining reliability.
Solution Approach 2:
The patent employs monoclonal antibodies with optimized binding parameters to PVR. By carefully selecting and engineering antibodies with specific affinity and specificity parameters for PVR, the therapy achieves effective PVR-TIGIT blocking with minimal off-target effects, reducing the need for complex combination therapies and lowering overall treatment complexity.
2Reliability
If high-affinity monoclonal antibodies are developed to block PVR-TIGIT interaction, then T cell proliferation and NK cell activation are enhanced, but manufacturing precision and production difficulty increase
Solution Approach 1:
The patent develops monoclonal antibodies that serve multiple functions: they block PVR-TIGIT interaction to enhance immune activation, and their high-affinity binding to PVR provides both therapeutic efficacy and a reliable diagnostic marker. This multi-functionality reduces the need for separate diagnostic and therapeutic agents, simplifying manufacturing requirements while maintaining high reliability for both T cell proliferation and NK cell activation.
Solution Approach 2:
The patent uses hybridoma technology to create identical copies of the antibody-producing B cells, ensuring that each batch of monoclonal antibodies is precisely identical in structure and function. This copying approach ensures consistent manufacturing precision while maintaining the high affinity and specificity required for effective T cell proliferation and NK cell activation.
3Object-generated harmful factors
If antibodies are used to block PVR-TIGIT binding, then tumor cell viability is reduced through immune activation, but specificity to human PVR must be maintained to avoid off-target effects
Solution Approach 1:
The patent engineers monoclonal antibodies with highly specific local binding properties to human PVR. By optimizing the antigen-binding region of the antibodies to recognize unique epitopes on human PVR that are not present or differ in other species, the therapy achieves high specificity. This local quality control ensures that the antibodies block PVR-TIGIT interaction on human tumor cells while avoiding off-target effects on non-human cells or normal human cells with low PVR expression.
Solution Approach 2:
The patent performs preliminary validation to ensure that the monoclonal antibodies specifically recognize and block human PVR before clinical use. Through preclinical studies and specificity testing, the antibodies are validated to selectively target human PVR-expressing tumor cells while sparing normal cells and non-human cells, thereby preventing off-target effects while effectively reducing tumor cell viability through immune activation.
Data Source
AI summary
The present invention provides monoclonal antibodies that recognize poliovirus receptor (PVR) and inhibit its binding to T cell immunoreceptor with Ig and ITIM domains (TIGIT). The present invention further provides pharmaceutical compositions comprising the antibodies and methods for their use in cancer immunotherapy, treating infections and in diagnosis.