Anti-PD-1 Monoclonal Antibody Affinity Maturation
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Solution Overview
Problem
Current monoclonal antibody therapies for PD-1/PD-L1 signaling pathway, while showing promise in cancer treatment, require further development of human anti-PD-1 monoclonal antibodies with enhanced affinity and specificity to broaden clinical applications.
Innovation Solution
Development of human anti-PD-1 monoclonal antibodies, such as DFPD1-1, through a method involving biopanning of a synthetic ScFv phage library, followed by computer-aided design to create mutant libraries for CDR regions, resulting in higher affinity antibodies like DFPD1-3 and DFPD1-7, and subsequent cloning into eukaryotic expression vectors for production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional monoclonal antibody therapies are used for PD-1/PD-L1 signaling pathway, then cancer treatment shows promise, but affinity and specificity need enhancement to broaden clinical applications
Solution Approach 1:
The patent applies parameter changes by systematically mutating the CDR regions (complementary determining regions) of the antibody to optimize binding parameters. Through computer-aided design, the patent modifies amino acid sequences in the CDR1, CDR2, and CDR3 regions to enhance affinity and specificity for PD-1, thereby improving reliability while maintaining broad clinical applicability
Solution Approach 2:
The patent segments the antibody into functional regions, specifically focusing on the CDR regions (CDR1, CDR2, CDR3) for mutation and optimization. By separately designing and testing mutant libraries for each CDR region, the patent achieves enhanced affinity and specificity while maintaining the overall antibody structure and functionality for broad clinical use
Data Source
AI summary
The invention provides human monoclonal antibodies that specifically bind to PD-1 with high affinity. The anti-PD-1 monoclonal antibodies were screened from a synthetic antibody library, and affinity maturation was performed. The synthetic antibody libraries used to select for the high affinity anti-PD-1 monoclonal antibodies were made by replacing the light chain CDR1, CDR2 and CDR3 and heavy chain CDR1, CDR 2 and CDR 3 of phage libraries from the preliminary screening, and the high affinity anti-PD-1 monoclonal antibodies were selected. The human anti-PD-1 monoclonal antibodies have high affinity and inhibit the binding of PD-1 to its ligand PD-L1. The antibodies can be used for treating tumor, inflammation and autoimmune diseases.