Single Chain Polypeptides for Dual Antigen Targeting
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Solution Overview
Problem
Current therapies lack effective and specific mechanisms for targeting and interacting with effector and target cell antigens, particularly in the context of tumor microenvironments.
Innovation Solution
Development of single chain polypeptides comprising variable domains connected by linkers that fold into a conformation forming effector cell antigen interacting domains, which are linked to target cell antigen interacting domains, including VHH single domain antibodies, to specifically bind to tumor antigens and effector cell antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used, then treatment is provided, but they lack effective and specific mechanisms for targeting and interacting with effector and target cell antigens
Solution Approach 1:
The single chain polypeptide is segmented into distinct functional domains: effector cell antigen interacting domains (comprising variable domains connected by linkers that fold into specific conformations) and target cell antigen interacting domains (including VHH single domain antibodies). This segmentation allows each domain to independently perform its specific function while maintaining overall molecular integrity, thereby achieving both reliable targeting and specific interaction mechanisms.
Solution Approach 2:
Different regions of the single chain polypeptide are designed with distinct local qualities: the effector cell antigen interacting domains contain variable domains with specific folding patterns for binding effector cells, while the target cell antigen interacting domains contain VHH domains for binding target antigens. This local differentiation enables the molecule to simultaneously engage multiple cell types with high specificity through locally optimized binding interfaces.
2Reliability
If single chain polypeptides with multiple domains are developed, then specific cellular interactions are enhanced, but molecular complexity increases
Solution Approach 1:
Multiple functional domains that would traditionally require separate molecules are merged into a single chain polypeptide structure. The effector cell antigen interacting domains and target cell antigen interacting domains are covalently linked in a single polypeptide chain, enabling simultaneous engagement of effector cells and target antigens while simplifying the overall system architecture compared to using multiple separate therapeutic agents.
Solution Approach 2:
The single chain polypeptide is designed as a multi-functional molecule that can simultaneously interact with effector cell antigens and target cell antigens. This universal design allows a single therapeutic agent to perform multiple functions: binding to effector cells via variable domains, binding to target antigens via VHH domains, and facilitating the therapeutic interaction between these cell types, thereby reducing the need for multiple separate therapeutic molecules.
Data Source
AI summary
Described herein are single chain polypeptide compositions comprising variable domains connected by linkers that fold into a conformation such that the variable domains form two effector cell antigen interacting domains (E) wherein each effector cell antigen interacting domain comprises two variable domains of a single chain variable fragment (EV and EV), and at least one of the effector cell antigen interacting domains is linked to one or more target interacting domains. Also described herein are methods of use of the single chain polypeptides.