B7-H3 Cyclic Peptide Constructs for Cancer Therapy and Imaging
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Solution Overview
Problem
Current cancer treatments targeting B7-H3 are inadequate, necessitating the development of effective therapies that can specifically target this immune checkpoint molecule to inhibit cancer progression and improve patient outcomes.
Innovation Solution
Development of cyclic peptides that bind to B7-H3, optionally linked to a chelating agent for association with radionuclides, which can be used for targeted cancer therapy and imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer treatments are used, then cancer progression is not effectively inhibited, but developing new therapies increases complexity and time requirements
Solution Approach 1:
The patent modifies the molecular structure of peptides by changing parameters such as amino acid sequences, cyclic configurations, and linker lengths to optimize B7-H3 binding affinity. This systematic parameter optimization enables effective cancer treatment while maintaining manageable development complexity through structured molecular design approaches.
Solution Approach 2:
The therapeutic construct is segmented into distinct functional components: targeting moiety (cyclic peptide), linker, and chelating agent. This segmentation allows independent optimization of each component's function while simplifying the overall development process through modular assembly, resolving the contradiction between treatment efficacy and development complexity.
2Reliability
If B7-H3 targeting therapy is developed, then cancer cell survival is reduced, but treatment specificity and safety margins are challenging to achieve
Solution Approach 1:
The cyclic peptide targeting moiety is designed with specific local structural features and amino acid compositions that confer high affinity and specificity for B7-H3. This local quality optimization ensures accurate cancer cell targeting while minimizing off-target effects, as the peptide structure is precisely tailored to recognize only the B7-H3 antigen.
Solution Approach 2:
The patent employs synthesized cyclic peptide analogs that replicate and optimize the binding interface with B7-H3. By creating multiple peptide variants through systematic copying and modification of the core structure, the therapy achieves high targeting accuracy while the ability to select optimal variants helps avoid off-target effects.
3Manufacturing precision
If cyclic peptides are synthesized and optimized, then binding affinity to B7-H3 is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The patent employs dynamic optimization of peptide parameters during synthesis, allowing flexible adjustment of amino acid sequences, cyclic configurations, and linker structures. This dynamic approach enables achieving high binding affinity through iterative design and synthesis, while the modular nature of the constructs maintains manufacturability through standardized synthesis protocols.
Solution Approach 2:
The therapeutic construct is designed as a composite molecule combining cyclic peptide, linker, and chelating agent components. This composite approach allows each component to be synthesized using established methods, with the overall assembly following predictable conjugation chemistry, thereby maintaining manufacturing precision for high affinity binding while controlling synthesis complexity through modular composite construction.
4Adaptability or versatility
If radionuclide-chelator- peptide constructs are developed, then targeted imaging and therapy are enabled, but construct complexity and regulatory requirements increase
Solution Approach 1:
The construct design incorporates universal components that can be applied to both imaging and therapy functions. The cyclic peptide and chelating agent serve dual purposes: the peptide provides targeting for both modalities, and the chelator can bind different radionuclides for either diagnostic or therapeutic applications. This multi-functionality enables versatile imaging and therapy capability while managing construct complexity through shared structural elements.
Solution Approach 2:
The chelating agent acts as an intermediary component that bridges the cyclic peptide targeting moiety and the radionuclide. This intermediary design simplifies the overall construct architecture by providing a standardized connection interface, thereby enabling versatile imaging and therapy applications while reducing the complexity of direct radionuclide-peptide conjugation and meeting regulatory requirements through well-defined construct architecture.
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 target B7-H3-expressing cancer cells, providing therapeutic and imaging options, enhancing treatment efficacy and patient survival.
Implementation Method 1
cyclic peptides that bind to B7-H3
Implementation Method 2
targeting moieties such as peptides, proteins and antibodies that can bind to B7-H3
Implementation Method 3
attached, via an optional linker, to a chelating agent for association of a radionuclide
Data Source
AI summary
The present disclosure relates to targeting moieties such as peptides that can bind to B7-H3. 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.