Anti-CD73 Antibody Eliminating Hook Effect
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Solution Overview
Problem
Existing anti-CD73 monoclonal antibodies suffer from the 'hook effect,' where therapeutic efficacy decreases with increasing antibody concentration, making it difficult to determine optimal dosages and hindering effective treatment of tumor-related diseases.
Innovation Solution
A novel anti-human CD73 monoclonal antibody, 7-C10-Ba-C2, is developed using hybridoma cells from BABL/c mice immunized with human CD73 protein, featuring unique heavy-chain and light-chain sequences that avoid the hook effect, with high affinity and effective inhibition of CD73 enzyme activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-CD73 monoclonal antibodies are used, then CD73 binding activity is achieved, but the hook effect occurs causing decreased therapeutic efficacy at higher concentrations
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of the antibody (specifically in the CDR regions) to alter its binding characteristics. This changes the fundamental parameters of antibody-antigen interaction to eliminate the hook effect while maintaining therapeutic efficacy across a broader dosage range
2Quantity of substance
If antibody concentration is increased to improve therapeutic effect, then binding activity increases, but the hook effect causes therapeutic effect to decrease
Solution Approach 1:
The patent changes the binding parameters of the antibody through sequence modification, creating a new parameter regime where therapeutic effect continues to increase or plateau with dosage rather than decreasing. This allows reliable therapeutic effect across varying concentrations
3Manufacturing precision
If existing anti-CD73 antibodies are used, then CD73 inhibition is achieved, but optimal dosage determination becomes difficult due to the hook effect
Solution Approach 1:
By changing the antibody's binding parameters through sequence optimization, the patent creates a more predictable dose-response relationship. This makes it easier to identify and measure the optimal dosage point, improving both manufacturing precision and clinical dosing accuracy
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 antibody demonstrates high affinity for CD73, effective inhibition of enzyme activity without the hook effect, and significant tumor inhibition in animal models, providing a more suitable therapeutic option for tumor-related diseases.
Implementation Method 1
The binding kinetics of the monoclonal antibody was tested by the surface plasmon resonance (SPR) technique
Implementation Method 2
The inhibition effect of the monoclonal antibody on the enzyme activity of CD73 was tested
Implementation Method 3
The binding kinetics of the monoclonal antibody was tested by the surface plasmon resonance (SPR) technique
Implementation Method 4
The titers of the antibody in the serums of the immunized mice were determined by enzyme-linked immunosorbent assay (ELISA)
Data Source
AI summary
The present invention provides a novel anti-CD73 monoclonal antibody. The antibody has high affinity for human CD73 protein. Both biochemical-level and cell-level experiments show that the antibody is highly effective in inhibiting the enzyme activity of CD73. The in-vivo experiment indicates that the antibody has a significant inhibition effect on tumor cell growth. In particular, the antibody does not have the “hook effect” most prior art antibodies have in connection with inhibition of the enzyme activity of CD73, and is therefore more suitable for clinical use than the prior art antibodies.