Humanized Anti-PD-L1 Antibody for Specific, Stable PD-L1/PD-1 Blocking
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-PD-L1 antibodies face challenges in achieving high specificity, affinity, and stability, limiting their effectiveness in blocking the PD-L1/PD-1 signal pathway for treating tumors and viral infections.
Innovation Solution
Development of an anti-human PD-L1 humanized monoclonal antibody with specific sequences for the heavy and light chains (SEQ ID NO: 10 and 26) that enhances T-cell activation and inhibits tumor growth by specifically binding to PD-L1, using a combination of CDR-grafting and phage display to achieve high affinity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-PD-L1 antibodies are used, then the PD-L1/PD-1 signal pathway can be blocked, but the specificity, affinity, and stability are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure through humanization - changing the framework regions from murine to human sequences while preserving the CDR regions. This structural parameter change improves specificity and reduces immunogenicity, resolving the contradiction between maintaining blocking effectiveness and improving reliability.
Solution Approach 2:
The patent creates a humanized copy of the murine antibody by transferring the CDR sequences into a human antibody framework. This copying approach with selective modification preserves the antigen-binding capability (effectiveness) while improving specificity and reducing immune response against the therapeutic antibody.
2Reliability
If current anti-PD-L1 antibodies are used, then the PD-L1/PD-1 signal pathway can be blocked, but the affinity and stability are insufficient
Solution Approach 1:
The patent changes the stability parameters by humanizing the antibody framework regions, which improves the structural stability and reduces aggregation. The CDR regions are preserved to maintain high affinity binding to PD-L1, thus resolving the contradiction between stability and effectiveness.
3Reliability
If humanized monoclonal antibody is developed with specific sequences, then specificity and stability are enhanced, but the complexity of development increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody into functional regions - CDR regions for antigen binding and framework regions for structural stability. This segmentation allows independent optimization of each region, improving specificity through careful CDR selection while using standardized human frameworks to reduce development complexity.
Solution Approach 2:
The patent uses universal human antibody frameworks that can accommodate different CDR sequences. This multi-functionality approach allows the same human framework structure to support various antigen-specific CDRs, reducing the overall complexity of humanized antibody development while maintaining high specificity.
Data Source
Figure 1~2
Figure 3~4
Figure 5
AI summary
The present invention relates to the biomedicine field, in particular to an anti-human PD-L1 humanized monoclonal antibody and its applications. The invention obtains an anti-human PD-L1 humanized monoclonal antibody with good specificity, high affinity and stability by screening, and the antibody can specifically bind to human PD-L1 instead of binding to members of B7 family, and it can bind to active T-cells to strengthen the activation of T-cells, so it can significantly inhibit the growth of tumor.