Anti-PD-L1 Antibody CDR Engineering for High Affinity Binding
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Solution Overview
Problem
Existing anti-PD-L1 antibodies have low affinity and specificity for binding to PD-L1, which hinders their ability to effectively block the interaction between PD-L1 and PD-1, limiting their efficacy in tumor immunotherapy.
Innovation Solution
Development of an anti-PD-L1 antibody with specific Complementarity Determining Regions (CDRs) that demonstrate high affinity and specificity for binding to PD-L1, capable of blocking the PD-1/PD-L1 interaction and stimulating cytokine production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-PD-L1 antibodies are used, then the interaction between PD-L1 and PD-1 can be blocked, but the binding affinity and specificity are insufficient
Solution Approach 1:
The patent applies parameter changes by optimizing the antibody's Complementarity Determining Regions (CDRs) to achieve high binding affinity (KD < 10^-9 M) and specificity for PD-L1. The antibody includes specific CDR sequences (HCDR1: SEQ ID NO:37, HCDR2: SEQ ID NO:38, HCDR3: SEQ ID NO:39, LCDR1: SEQ ID NO:40, LCDR2: SEQ ID NO:41, LCDR3: SEQ ID NO:42) that were engineered to enhance binding characteristics while maintaining blocking capability.
2Reliability
If existing anti-PD-L1 antibodies are used, then the interaction between PD-L1 and PD-1 can be blocked, but the binding specificity is insufficient
Solution Approach 1:
The patent applies local quality by designing the antibody with specific CDR regions that provide both high affinity and specificity for PD-L1. The CDRs are engineered to recognize specific epitopes on PD-L1, ensuring the antibody binds selectively to PD-L1 rather than cross-reacting with other proteins, thereby achieving both high blocking capability and specificity.
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 effectively blocks the PD-1/PD-L1 interaction and stimulates cytokine production, offering improved therapeutic potential for PD-L1-mediated diseases, as demonstrated by its high binding affinity and biological function in vitro and in vivo.
Implementation Method 1
The antibody includes the following Complementarity Determining Regions (CDRs): an HCDR1 as shown in an amino acid sequence, which is shown as any one of SEQ ID NO.37, 19, 31 or 25 or has at least 95% identity to a sequence as shown in any one of SEQ ID NO.37, 19, 31 or 25; an HCDR2 as shown in an amino acid sequence, which is shown as any one of SEQ ID NO.38, 20, 32 or 26 or has at least 95% identity to a sequence as shown in any one of SEQ ID NO.38, 20, 32 or 26; an HCDR3 as shown in an amino acid sequence, which is shown as any one of SEQ ID NO.39, 21, 33 or 27 or has at least 95% identity to a sequence as shown in any one of SEQ ID NO.39, 21, 33 or 27; an LCDR1 as shown in an amino acid sequence, which is shown as any one of SEQ ID NO.40, 22, 34 or 28 or has at least 95% identity to a sequence as shown in any one of SEQ ID NO.40, 22, 34 or 28; an LCDR2 as shown in an amino acid sequence, which is shown as any one of SEQ ID NO.41, 23, 35 or 29 or has at least 95% identity to a sequence as shown in any one of SEQ ID NO.41, 23, 35 or 29; and an LCDR3 as shown in an amino acid sequence, which is shown as any one of SEQ ID NO.42, 24, 36 or 30 or has at least 95% identity to a sequence as shown in any one of SEQ ID NO.42, 24, 36 or 30.
Implementation Method 2
The antibody effectively blocks the PD-1/PD-L1 interaction and stimulates cytokine production, offering improved therapeutic potential for PD-L1-mediated diseases
Data Source
AI summary
The present disclosure relates to the field of biomedicine, in particular to an anti-PD-L1 antibody and the use thereof. The anti-PD-L1 antibody or the antigen-binding fragment thereof provided in the present disclosure binds to a PD-L1 protein with a high affinity and high specificity, can effectively block the interaction between PD-L1 expressed on a cell surface and PD-1, and has the biological function activity of stimulating the production of cytokine, and has wide application prospects.