Anti-LAG3 Antibody Engineering for Higher Binding Affinity
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Solution Overview
Problem
There is a need for effective treatments based on LAG3, particularly anti-LAG3 antibodies, that exhibit higher affinity binding to their target antigen and improved cell killing capabilities compared to existing antibodies.
Innovation Solution
Development of fully human anti-LAG3 antibodies with engineered heavy and light chain variable regions, featuring specific CDR sequences, to enhance antigen binding, cell activation, and cytokine release capabilities, with affinities as low as 10−8 M or less.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-LAG3 antibodies are used, then basic therapeutic effect is achieved, but binding affinity and cell killing capability are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences in the variable regions of the antibody heavy and light chains. Specifically, the engineered antibodies contain modified CDR regions (Complementarity Determining Regions) with altered amino acid compositions that increase binding affinity to LAG3. This includes changes to key residues in CDR-H3 and CDR-L3 regions, which directly contact the antigen, thereby enhancing the strength of the antibody-antigen interaction while maintaining therapeutic reliability.
2Reliability
If existing anti-LAG3 antibodies are used, then basic immune modulation is achieved, but cytokine release and T cell activation are insufficient
Solution Approach 1:
The patent employs parameter changes by optimizing the Fc region constant domains (CH2 and CH3 regions) to enhance effector functions. The engineered antibodies incorporate specific amino acid modifications in the Fc region that increase binding affinity to Fcγ receptors on immune cells, thereby amplifying cytokine release and T cell activation responses. This includes modifications to glycosylation sites and amino acid residues that influence Fc receptor engagement, leading to enhanced immune productivity while maintaining reliable immune modulation.
Data Source
AI summary
The present disclosure provides fully human anti-LAG3 IgG class antibodies engineered to have amino acid sequence in their heavy chain variable region and/or light chain variable region to improve antigen binding, cell binding, T cell activation and cytokine release capabilities.