Antibody CDR Insertion for Alpha-v-beta-6 Integrin Specificity
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Solution Overview
Problem
Current antibodies lack specificity for targeting αvβ6 integrin, which is overexpressed in various cancers and plays a role in tumor invasion and metastasis, limiting their effectiveness in cancer therapy and diagnosis.
Innovation Solution
Development of antibodies by inserting an amino acid sequence capable of binding to αvβ6 into the complementarity determining region (CDR) of a parent antibody, such as MFE-23, to modify its binding specificity while retaining stability and immune system interaction properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptides are used to target αvβ6 integrin, then binding specificity is achieved, but stability and half-life are insufficient
Solution Approach 1:
The patent combines the target-specific peptide sequence (RGDLXXL/I motif) with the stable antibody framework structure. This merging allows the antibody to provide both the binding specificity of the peptide and the stability/half-life of the antibody, resolving the contradiction between specificity and durability.
Solution Approach 2:
The invention creates a composite molecular structure by inserting the peptide sequence into the complementarity determining region (CDR) of the antibody. This composite structure integrates the functional properties of both peptides (specificity) and antibodies (stability), achieving both binding specificity and extended half-life.
2Stability of the object's composition
If antibodies are used for cancer therapy, then stability and immune interaction are improved, but specificity for αvβ6 integrin is insufficient
Solution Approach 1:
The patent applies local quality by inserting the αvβ6-specific peptide sequence (RGDLXXL/I) specifically into the complementarity determining region (CDR) of the antibody. This localized modification ensures that only the binding region acquires the new specificity while the rest of the antibody maintains its stable structure and immune interaction properties.
Solution Approach 2:
The modified CDR region acts as an intermediary that bridges the stable antibody framework and the target-specific peptide function. By inserting the peptide sequence into the CDR, the antibody serves as a mediator that provides both structural stability and specific binding capability to αvβ6 integrin.
3Reliability
If peptide sequences are used to bind αvβ6, then binding capability is achieved, but immunogenicity increases
Solution Approach 1:
The patent uses the antibody framework as a template or copy structure to present the peptide sequence in a context that reduces immunogenicity. The humanized antibody framework provides a familiar, low-immunogenicity background that carries the binding-specific peptide sequence, thereby maintaining binding capability while minimizing immune recognition of the peptide as foreign.
Data Source
AI summary
The present invention relates to antibodies that are obtained by inserting an amino acid sequence capable of binding to a target into the complementarity determining region (CDR) of a parent antibody. The antibody thus obtained has a new binding specificity. For example, the antibodies of the present invention are able to bind to the target, such as αvβ6 integrin, while retaining one or more of the useful properties of the parent antibody.