Humanized Anti-CD73 Antibody Inhibits Tumor Metastasis
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Solution Overview
Problem
Current cancer therapies lack effective methods to inhibit the catalytic activity of CD73, a rate-limiting enzyme that promotes tumor growth and metastasis by suppressing adaptive anti-tumor immune responses, particularly in cancer cells that express high levels of CD73.
Innovation Solution
Development of a humanized 1E9 antibody with specific variable regions that target and inhibit CD73, including a light chain with mouse CDR L1, L2, or L3 and a heavy chain with mouse CDR H1, H2, or H3, designed to bind to the CD73 antigen, thereby inhibiting its catalytic activity and preventing metastasis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer therapies are used, then general tumor treatment is provided, but they fail to effectively inhibit CD73 catalytic activity and prevent metastasis
Solution Approach 1:
The patent modifies the antibody structure by humanizing the 1E9 antibody variable regions while maintaining mouse CDR sequences, changing the immunogenicity parameters to reduce human immune system rejection while preserving CD73 binding affinity and catalytic inhibition capability
Solution Approach 2:
The patent creates a humanized version of the mouse 1E9 antibody by copying the essential CDR sequences that recognize CD73 and grafting them into human antibody framework regions, thereby replicating the binding function while adapting to human physiology
2Measurement precision
If mouse antibodies are used to target CD73, then high binding affinity is achieved, but human immune system rejection occurs
Solution Approach 1:
The patent applies local quality by maintaining mouse CDR sequences (the local binding region) while replacing the human framework regions, thereby preserving high binding affinity at the antigen-binding site while reducing overall immunogenicity of the antibody molecule
Solution Approach 2:
The patent segments the antibody into distinct functional regions: mouse CDR sequences for antigen binding and human framework regions for reduced immunogenicity, allowing each segment to perform its optimized function independently
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 humanized 1E9 antibody effectively inhibits CD73 activity, reducing tumor growth and metastasis by enhancing anti-tumor immune responses, as demonstrated by its ability to relieve AMP-dependent suppression of T cell proliferation and IFN-gamma secretion.
Implementation Method 1
a humanized 1E9 antibody with specific variable regions that target and inhibit CD73, including a light chain with mouse CDR L1, L2, or L3 and a heavy chain with mouse CDR H1, H2, or H3, designed to bind to the CD73 antigen
Implementation Method 2
The humanized 1E9 antibody effectively inhibits CD73 activity, reducing tumor growth and metastasis by enhancing anti-tumor immune responses, as demonstrated by its ability to relieve AMP-dependent suppression of T cell proliferation and IFN-gamma secretion
Data Source
AI summary
Provided herein are, inter alia, humanized 1E9 antibodies capable of binding CD73. The humanized antibodies are useful for the treatment of cancer. Further provided are nucleic acids encoding humanized 1E9 antibodies and methods of inhibiting cell proliferation using the humanized antibodies provided herein.