CD47 Antigen-Binding Molecules Optimizing Phagocytosis
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Solution Overview
Problem
Current antibody technologies targeting CD47-SIRPα interaction have limitations in affinity and efficacy for inhibiting tumor cell phagocytosis, with existing anti-CD47 antibodies showing suboptimal binding and phagocytic enhancement.
Innovation Solution
Development of antigen-binding molecules with specific VH and VL regions that bind to CD47 with high affinity, inhibiting the CD47-SIRPα interaction and enhancing phagocytosis of CD47-expressing cells, including variants with amino acid substitutions for improved binding and functional properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high-affinity anti-CD47 antibodies are used to block CD47-SIRPα interaction, then phagocytosis of tumor cells is enhanced, but hemagglutination occurs as a harmful side effect
Solution Approach 1:
The patent applies parameter changes by modifying the affinity of the antigen-binding molecule for CD47. Instead of using very high-affinity antibodies that cause hemagglutination, the invention uses molecules with optimized, moderate affinity that effectively block the CD47-SIRPα interaction and enhance phagocytosis without inducing hemagglutination. This is achieved through selective affinity optimization to distinguish between therapeutic efficacy and harmful side effects.
2Reliability
If existing anti-CD47 antibodies are used, then some binding to CD47 is achieved, but binding affinity and phagocytic enhancement are suboptimal
Solution Approach 1:
The patent optimizes the binding affinity parameter of anti-CD47 molecules to achieve optimal phagocytic enhancement. By systematically adjusting and selecting antigen-binding molecules with specific affinity ranges, the invention achieves superior phagocytic enhancement compared to existing antibodies, resolving the contradiction between adequate binding and effective phagocytosis promotion.
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 antigen-binding molecules demonstrate enhanced binding to CD47 and more potent inhibition of the CD47-SIRPα interaction compared to prior art antibodies, leading to increased phagocytosis of CD47-expressing cells and potential therapeutic efficacy in cancer treatment.
Implementation Method 1
an antigen-binding molecule, optionally isolated, which is capable of binding to CD47
Data Source
AI summary
CD47 antigen-binding molecules are disclosed. Also disclosed are nucleic acids and expression vectors encoding, compositions comprising, and methods using, the CD47 antigen-binding molecules.