Anti-GPC3 Antibody CDR Sequences Enhance ADCC and CDC
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Solution Overview
Problem
Conventional anti-glypican 3 antibodies have limited antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities, which are essential for effective anticancer therapy.
Innovation Solution
Development of antibodies with specific heavy and light chain variable regions, including CDR sequences that enhance ADCC and CDC activities, allowing for higher cytotoxicity against cells expressing glypican 3.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-glypican 3 antibodies are used, then the antibody can bind to GPC3, but the ADCC and CDC activities are limited
Solution Approach 1:
The patent applies parameter changes by modifying the antibody's CDR sequences (specifically CDR1, CDR2, and CDR3 of the heavy chain variable region) to optimize binding affinity and cytotoxicity activities. Different CDR combinations ( SEQ ID NOs: 103-136) are presented as alternative parameter sets that enhance ADCC and CDC activities while maintaining GPC3 specificity
Solution Approach 2:
The patent creates composite antibody structures by combining specific heavy chain variable regions with specific light chain variable regions ( SEQ ID NOs: 137-171). This composite approach allows optimization of both binding properties and cytotoxicity functions through the synergistic combination of different CDR sequences from heavy and light chains
2Reliability
If conventional anti-glypican 3 antibodies are used, then the antibody structure is simpler, but the cytotoxicity activity is lower
Solution Approach 1:
The patent modifies key parameters of the antibody structure, specifically the CDR sequences in the heavy chain variable region ( SEQ ID NOs: 103-136), to enhance cytotoxicity activity. These parameter changes are designed to improve ADCC and CDC functions while maintaining manufacturability through defined sequence variations
Data Source
AI summary
An antibody capable of binding to a specific region of glypican 3, as well as a humanized antibody created based on that antibody are disclosed. The anti-GPC3 antibody of the invention has a higher ADCC activity and CDC activity compared with those of a conventional antibody. The antibody of the present invention is useful as a cell growth inhibitor, an anticancer agent and an agent for diagnosis of cancers.