LAG-3 Monoclonal Antibody CDR Optimization for High Affinity
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Solution Overview
Problem
Current LAG-3 antibodies have limited activity and wide indications, necessitating the development of antibodies with higher affinity and yield for improved therapeutic and detection effects in cancer immunotherapy.
Innovation Solution
Development of an LAG-3 antibody with high affinity and specificity, featuring specific heavy and light chain variable regions with complementary determining regions (CDRs) that retain binding affinity, allowing for the creation of chimeric, humanized, or fully human monoclonal antibodies capable of inhibiting tumor growth and metastasis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current LAG-3 antibodies are used, then the basic blocking function is achieved, but the binding affinity is insufficient and therapeutic efficacy is limited
Solution Approach 1:
The patent applies parameter changes by optimizing the antibody's binding parameters through specific amino acid mutations in the complementarity determining regions (CDRs). The heavy chain CDRs (SEQ ID NOs: 8n+2, 8n+3, 8n+4) and light chain CDRs (SEQ ID NOs: 8n+6, 8n+7, 8n+8) are designed with specific sequences that enhance binding affinity to LAG-3, achieving nanomolar affinity levels that significantly improve therapeutic efficacy compared to conventional antibodies
2Productivity
If existing LAG-3 antibodies are used, then some therapeutic effect is observed, but the yield is low and production efficiency is poor
Solution Approach 1:
The patent employs copying principles by creating recombinant antibody molecules through genetic engineering. The optimized CDR sequences are cloned into expression vectors and expressed in host cells (such as CHO cells), enabling large-scale production of the antibody. This recombinant approach allows for consistent, high-yield production that overcomes the limitations of traditional antibody production methods
3Reliability
If conventional antibody development approaches are used, then basic functionality is achieved, but the specificity and activity are insufficient for wide indications
Solution Approach 1:
The patent achieves universality by designing an antibody with highly specific binding to LAG-3 that can effectively block the receptor across different tissue types and disease states. The optimized CDR sequences enable the antibody to maintain high specificity and activity in various cancer types and non-cancer applications, providing a universal platform for multiple indications including cancer immunotherapy, autoimmune disease modulation, and diagnostic applications
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 antibodies demonstrate strong affinity for LAG-3, effectively blocking its interaction with ligands like MHC II and LSECtin, enhancing T-cell activation and immunotherapy efficacy, with potential applications in various cancers.
Implementation Method 1
the heavy chain variable region comprises the following three complementary determining regions or CDRs: CDR1 shown in SEQ ID NO: 8n+2, CDR2 shown in SEQ ID NO: 8n+3, and CDR3 shown in SEQ ID NO:8n+4
Data Source
AI summary
Disclosed in the present invention are an antibody targeting LAG-3, a preparation method therefor and the use thereof. In particular, disclosed in the present invention is a novel monoclonal antibody targeting LAG-3. Also disclosed in the present invention is a method for the preparation of the monoclonal antibody. The monoclonal antibody of the present invention is capable of binding LAG-3 antigens with high specificity, and has very high affinity and significant activities such as anti-tumor activity.