CCR8 Monoclonal Antibodies Using Native-Conformation Immunization
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Solution Overview
Problem
Existing methods for generating antibodies targeting CCR8, a chemokine receptor, face challenges in maintaining its native configuration post-purification, leading to antibodies with reduced recognition capability and insufficient immune response, necessitating improved immunization strategies.
Innovation Solution
The development of novel CCR8 antibodies through animal immunization using DNA plasmids, mRNA encoding CCR8, and cells overexpressing CCR8, resulting in antibodies with enhanced binding ability, specificity, and cytotoxicity against CCR8+ cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If CCR8 is purified for antibody generation, then it can be used as an antigen, but it loses its native configuration and cannot elicit high-quality antibodies
Solution Approach 1:
The patent uses eukaryotic expression systems (insect cells, mammalian cells) as intermediaries to produce CCR8 protein that maintains its native conformation. These expression systems act as mediators between the purified CCR8 antigen and the immunization process, ensuring the antigen retains its native structure for effective antibody generation.
Solution Approach 2:
The patent changes the production parameters of CCR8 by using different expression systems (insect cells vs. mammalian cells) and purification conditions. By optimizing expression parameters and purification protocols, the patent maintains the native configuration of CCR8 while still enabling its use as an immunogen.
2Ease of manufacture
If DNA molecules are used for immunization, then the process is simplified, but the immune response is insufficient
Solution Approach 1:
The patent combines DNA immunization with protein immunization strategies by using eukaryotic expression systems that produce both the antigen protein and stimulate immune response. This merged approach integrates the simplicity of DNA-based methods with the effectiveness of protein-based immunization.
Solution Approach 2:
The eukaryotic expression system acts as an intermediary that converts DNA into functional protein antigen within the host, thereby enhancing the immune response while maintaining the ease of DNA-based delivery and expression.
3Ease of manufacture
If peptides are used as antigens, then immunization is easier, but the resulting antibodies lack recognition capability for natural targets
Solution Approach 1:
The patent uses eukaryotic expression systems as intermediaries to produce full-length CCR8 protein with native conformation. This intermediary approach ensures that the antigen presented to the immune system is the complete, properly folded receptor rather than truncated peptides, thereby generating antibodies with authentic recognition capability.
Solution Approach 2:
The patent changes the antigen form from peptides to full-length native protein by modifying the expression and purification parameters. This parameter change ensures the antigen maintains its native structure while still being producible through controlled laboratory processes.
Data Source
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AI summary
The present application relates to a monoclonal antibody that specifically binds to CCR8 or an antigen-binding portion thereof. The present application also relates to a nucleic acid molecule encoding the antibody or the antigen-binding portion thereof; an expression vector, host cell and method for expressing the antibody or the antigen-binding portion thereof; and a therapeutic method using the antibody or the antigen-binding portion thereof, the nucleic acid molecule, the expression vector and/or the host cell.