DLL3-Targeting Cyclic Peptide Constructs for Cancer Therapy
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Solution Overview
Problem
Current targeted radionuclide therapies for cancer lack effective targeting moieties that specifically bind to delta-like ligand 3 (DLL3), a protein highly expressed in various cancer types, limiting their therapeutic efficacy.
Innovation Solution
Development of cyclic peptides that specifically target DLL3, which are attached to a chelating agent via an optional linker, allowing for labeling with radionuclides or cytotoxic agents, thereby facilitating targeted delivery to cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional targeted radionuclide therapies are used, then cancer treatment is provided, but effective targeting to DLL3-expressing cancer cells is insufficient
Solution Approach 1:
The patent modifies the chemical structure of peptides by changing parameters such as amino acid sequences, cyclic configurations, and linker structures to optimize binding affinity and specificity for DLL3. This allows the targeting moiety to effectively distinguish and bind to DLL3-expressing cancer cells while minimizing off-target effects.
Solution Approach 2:
The invention creates composite targeting constructs by combining peptide targeting moieties with chelating agents and radionuclides. This composite approach integrates multiple functional elements (targeting, chelation, and therapeutic payload) into a single coordinated system that enhances both specificity and therapeutic efficacy.
2Measurement precision
If peptide targeting moieties are developed, then specific binding to DLL3 is achieved, but the complexity of construct design increases
Solution Approach 1:
The patent divides the targeting construct into distinct functional segments: the peptide targeting moiety responsible for DLL3 binding, the chelating agent for radionuclide coordination, and the linker for structural connection. This segmentation allows each component to be optimized independently while simplifying the overall design and assembly process.
Solution Approach 2:
The linker acts as an intermediary element between the peptide and chelating agent, providing a flexible connection that maintains the spatial relationship between functional groups while allowing for conformational flexibility. This intermediary component simplifies the integration of multiple functional elements without compromising binding specificity.
3Productivity
If radionuclide labeling is implemented, then targeted therapy delivery is enabled, but the risk of harm to healthy tissues increases
Solution Approach 1:
The patent employs peptide sequences and structural features that create local quality differences in binding affinity and cellular internalization. This allows the construct to preferentially target DLL3-expressing cancer cells over healthy tissues, enhancing therapeutic delivery efficiency while minimizing collateral damage through selective accumulation and uptake.
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 cyclic peptides effectively bind to DLL3-expressing cancer cells, enabling targeted delivery of therapeutic agents, such as radionuclides, which can selectively kill cancer cells while minimizing harm to healthy tissues.
Implementation Method 1
the cyclic peptide binds to DLL3
Implementation Method 2
attached, via an optional linker, to a chelating agent for labeling with a radionuclide
Data Source
AI summary
The present disclosure relates to targeting moieties such as peptides that can bind to DLL3. The disclosure also provides targeting constructs, which may include a targeting moiety attached, via an optional linker, to a chelating agent for association of a cargo. Methods of making the constructs and formulations thereof are also provided. Methods of using the constructs and/or formulations thereof to treat subjects, for example, to treat or prevent cancer, are also described.