CD70 Antibody Engineering for High-Affinity CD27 Blocking
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Solution Overview
Problem
Existing CD70 antibodies for therapeutic use exhibit suboptimal binding affinity and lack the ability to effectively block the CD70/CD27 interaction, limiting their efficacy in treating CD70-expressing cancers and immunological disorders.
Innovation Solution
Development of camelid-derived CD70 antibodies with extremely high binding affinity and specific epitope recognition, including humanised and chimeric variants, which exhibit off-rates of less than 7×10−4 s−1 and can block or not block the CD70/CD27 interaction, enabling enhanced therapeutic potential.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CD70 antibodies are used, then they can bind to CD70, but their binding affinity is suboptimal and they cannot effectively block the CD70/CD27 interaction
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure to achieve extremely high binding affinity (off-rate < 7×10^-4 s^-1). This is accomplished through camelid-derived antibody design with optimized variable domains, representing a fundamental change in the binding parameters compared to conventional antibodies. The structural modifications enable both high affinity binding and effective blocking of the CD70/CD27 interaction simultaneously.
2Reliability
If CD70 antibodies with high binding affinity are developed, then they show superior binding to cancer cell lines, but this requires complex camelid-derived antibody design
Solution Approach 1:
The patent extracts the essential binding function from conventional antibody structures and implements it through camelid-derived antibody domains. By focusing on the variable domains (VH and VL) of camelid antibodies, the invention achieves high binding affinity without requiring the full complexity of conventional mammalian antibody structures. This extraction approach simplifies the design while maintaining or enhancing binding performance.
3Ease of manufacture
If conventional antibodies are used for therapy, then they can be produced using standard methods, but they exhibit suboptimal therapeutic efficacy due to low binding affinity
Solution Approach 1:
The patent changes the fundamental parameters of antibody design by using camelid-derived domains instead of conventional mammalian antibody structures. This parameter change enables both high therapeutic efficacy through extremely high binding affinity and practical manufacturability through established recombinant expression systems. The camelid antibody format can be produced using standard mammalian cell culture methods, maintaining ease of manufacture while dramatically improving therapeutic efficacy.
Data Source
AI summary
The present invention relates to antibodies and antigen binding fragments thereof which bind to the human CD70 protein with high affinity and display potent inhibition of tumour cell growth.