4-1BB Antibody CDR3 Optimization for High Affinity Binding
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Solution Overview
Problem
Current 4-1BB antibodies lack high specificity and biological activity, and there is a need for a 4-1BB antibody with strong antigen binding activity and the ability to activate downstream signals effectively for the treatment of cancer and autoimmune diseases.
Innovation Solution
A high-affinity 4-1BB antibody with specific heavy and light chain variable regions, derived from human-derived sequences, is developed using transgenic mouse technology to enhance binding affinity and biological activity, significantly increasing IFN-γ and IL-2 expression in human T lymphocytes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing 4-1BB antibodies are used, then some basic binding activity is achieved, but antigen binding affinity and downstream signal activation are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the CDR3 region of the heavy chain variable region through amino acid substitutions, deletions, or additions. This targeted parameter change in the antigen-binding site directly improves antigen binding affinity while maintaining overall antibody structure simplicity, resolving the contradiction between binding reliability and structural complexity
Solution Approach 2:
The patent implements local quality by focusing modifications specifically on the CDR3 region of the heavy chain, which is a critical local site for antigen recognition and binding. By optimizing only this specific local region rather than the entire antibody molecule, the patent achieves improved binding affinity with minimal increase in overall structural complexity
2Reliability
If existing 4-1BB antibodies are used, then some T cell activation is achieved, but downstream signal activation and cytokine expression are insufficient
Solution Approach 1:
The patent applies parameter changes by optimizing the CDR3 region to enhance downstream signal activation capability. This modification changes the functional parameter of signal transduction efficiency, enabling stronger NF-κB pathway activation and increased cytokine expression (IFN-γ, IL-2) without complicating the signal pathway itself
Solution Approach 2:
The patent uses the CDR3 region as an intermediary element that mediates between the antibody binding event and downstream signal activation. By optimizing this intermediary region, the patent enhances the coupling efficiency between antigen binding and signal transduction, improving downstream activation without adding complexity to the signal pathways
3Reliability
If existing 4-1BB antibodies are used, then some therapeutic effect is achieved, but specificity and biological activity are insufficient for effective cancer and autoimmune disease treatment
Solution Approach 1:
The patent applies parameter changes by optimizing key parameters of the antibody sequence, particularly in the CDR3 region, to enhance therapeutic efficacy. This includes modifying amino acid sequences to improve both antigen binding affinity and biological activity, achieving better therapeutic outcomes without proportionally increasing sequence complexity
Solution Approach 2:
The patent implements local quality by focusing optimization on the CDR3 region, which is a critical local determinant of both binding specificity and biological activity. By improving this specific local region rather than the entire antibody sequence, the patent achieves enhanced therapeutic efficacy with minimal increase in overall sequence complexity
Data Source
AI summary
Provided in the present invention are a 4-1BB antibody and a preparation method and the use thereof. In particular, provided in the present invention are a 4-1BB antibody, which has high affinity to 4-1BB protein, can effectively activate the signal downstream of the 4-1BB and significantly increase expression quantities of IFN-γ and IL-2 in human mixed lymphocytes or T lymphocytes, and can be used to treat cancers and autoimmune diseases.