CD112R Antibodies Block Nectin-2 Binding for Cancer Immunotherapy
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Solution Overview
Problem
There is a need for more effective, specific, and stable agents that can potentiate immune cells to attack tumors or virus-infected cells, as current therapies face challenges in overcoming immune checkpoint barriers and achieving optimal anti-cancer immune responses.
Innovation Solution
Development of high-affinity monoclonal antibodies that specifically bind to CD112R, preventing its interaction with Nectin-2 and enhancing T and NK cell activities, which can be used alone or in combination with other immunomodulating agents to boost anti-cancer immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies target immune checkpoint molecules (e.g., PD-1, TIGIT) to inhibit tumor immune evasion, then anti-tumor immune response is enhanced, but the complexity of the therapeutic approach increases and optimal response is not always achieved
Solution Approach 1:
The invention segments the immune checkpoint inhibition strategy by targeting a specific subset of checkpoints (CD112R/PVRIG) rather than using broad-spectrum inhibitors. This focused approach simplifies the therapeutic mechanism while maintaining effectiveness, as CD112R is specifically expressed on tumor cells and inhibits T-cell activation through a defined pathway involving Nectin-2 binding
Solution Approach 2:
The patent identifies and targets the intermediary molecule CD112R (PVRIG) that mediates the inhibitory signal from tumors to T cells. By blocking this specific intermediary rather than directly attacking tumor cells or using broad immunosuppressants, the therapy achieves precise immune modulation with reduced complexity
2Reliability
If multiple immune checkpoint inhibitors are combined to overcome resistance, then anti-cancer activity increases, but side effects and safety issues worsen
Solution Approach 1:
The invention applies local quality by targeting CD112R specifically on tumor cells rather than affecting all immune cells systemically. This localized targeting reduces off-target effects and side effects while maintaining potent anti-tumor activity, as the antibody blocks the inhibitory signal only at the tumor cell surface where it is expressed
3Reliability
If existing anti-CD112R antibodies are used to block Nectin-2 binding, then T-cell proliferation is inhibited, but affinity and specificity to human CD112R are insufficient
Solution Approach 1:
The patent applies parameter changes by optimizing the antibody's binding parameters (affinity and specificity) through careful selection and engineering of the antibody sequence. The invention uses antibodies with defined binding characteristics that specifically recognize human CD112R with high affinity, improving upon prior art while maintaining the desired inhibitory function
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The antibodies effectively block CD112R-Nectin-2 interactions, restoring T and NK cell activities, and when combined with other agents, significantly increase anti-cancer activity, offering improved potency and specificity with reduced side effects.
Implementation Method 1
antibodies and fragments thereof which bind to the human protein CD112R (PVRIG)
Data Source
AI summary
The present invention provides monoclonal antibodies that recognize human CD 112R with high affinity and specificity and inhibit its binding to Nectin-2. The present invention further provides pharmaceutical compositions comprising the antibodies and methods for their use in cancer immunotherapy and in diagnosis.