Targeted ADAM17 Blocker Compounds for Immune Cell Function
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Solution Overview
Problem
Current therapies fail to effectively inhibit ADAM17 activity, which impairs immune cell function by cleaving CD16, reducing the efficacy of antibodies targeting tumor cells and potentially exacerbating infections like SARS-CoV-2, due to the lack of specific and efficient ADAM17 inhibitors.
Innovation Solution
Development of Targeted ADAM17 Blocker (TAB) compounds comprising an ADAM17-inhibiting domain linked with a targeting domain and a linker, specifically designed to bind to immune cells like NK cells, thereby inhibiting ADAM17 activity and enhancing immune cell function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to inhibit ADAM17 activity, then ADAM17 inhibition is attempted, but the inhibition is ineffective due to lack of specific and efficient inhibitors
Solution Approach 1:
The TAB compound is divided into distinct functional segments: a targeting domain (antibody or fragment) that binds to immune cells, a linker that connects the domains, and an ADAM17-inhibiting domain. This segmentation allows each component to be optimized independently for its specific function, resulting in a reliable ADAM17 inhibitor with improved efficacy compared to previous non-specific therapies.
2Reliability
If ADAM17 activity is inhibited, then immune cell function is enhanced, but the mechanism of action is unclear due to lack of specific inhibitors
Solution Approach 1:
The linker serves as an intermediary component that connects the targeting domain to the ADAM17-inhibiting domain while maintaining appropriate spatial orientation and distance. This intermediary structure enables the compound to selectively deliver inhibition to ADAM17 on immune cells, providing a clear mechanism of action where the targeting domain binds to cell surface markers, the linker positions the inhibitor, and the ADAM17-inhibiting domain blocks ADAM17 activity.
3Reliability
If ADAM17 is inhibited by current therapies, then some ADAM17 activity is blocked, but the inhibition is not specific to immune cells
Solution Approach 1:
The TAB compound exhibits local quality through its modular design where the targeting domain provides cell-type-specific localization. Different antibody variants can be selected to target specific immune cell populations (e.g., NK cells, T cells, macrophages), allowing the same ADAM17-inhibiting domain to be delivered selectively to different cell types. This enables tailored inhibition strategies for different immune cells while maintaining reliable ADAM17 blocking activity.
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 TAB compounds effectively inhibit ADAM17, enhancing NK cell proliferation and immune cell function, improving the recognition and elimination of tumor cells and potentially reducing morbidity and viral burden in SARS-CoV-2 infections.
Implementation Method 1
the targeting domain includes an antibody or a fragment thereof... the targeting domain selectively binds to an immune cell
Implementation Method 2
an ADAM17-inhibiting domain... effectively inhibit ADAM17, enhancing NK cell proliferation and immune cell function
Data Source
AI summary
Compounds that inhibit ADAM17 activity include a targeting domain that selectively binds to a target, an ADAM17-inhibiting domain, and a linker operably linking the targeting domain and the ADAM17-inhibiting domain. Compounds that bind to ADAM17 include one or more anti-ADAM17 binding domains that include one or more antibody fragments that bind to ADAM17. ADAM17-binding domains and/or ADAM17-inhibiting domains can be included in therapeutic compounds and/or compounds that detect ADAM17.