EL2-Binding CLDN6 Antibodies for Selective Tumor Growth Inhibition
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Solution Overview
Problem
Current cancer treatments using monoclonal antibodies are limited in their ability to effectively target and inhibit the growth of tumors, particularly those expressing Claudin-6 (CLDN6), leading to high cancer incidence and mortality rates.
Innovation Solution
Development of antigen-binding proteins that specifically bind to the extracellular domain of CLDN6, particularly Extracellular Loop 2 (EL2), inhibiting tumor growth without additional moieties, and inducing apoptosis, ADCC, CDC, or disrupting tumor cell adherence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional monoclonal antibodies are used for cancer treatment, then some cancer treatments are available, but the ability to effectively target and inhibit tumor growth is limited
Solution Approach 1:
The patent applies local quality by designing antibodies that specifically target the extracellular domain of Claudin-6, particularly the Extracellular Loop 2 region, which is uniquely expressed on certain cancer cell surfaces. This selective targeting enables effective tumor growth inhibition while minimizing off-target effects, directly resolving the contradiction between reliable tumor inhibition and adaptable targeting capability.
Solution Approach 2:
The patent utilizes parameter changes by modifying the binding characteristics of the antibody-antigen interaction. The antibody is engineered to bind with high affinity to specific epitopes on CLDN6, changing the binding parameters to achieve more effective tumor targeting compared to conventional antibodies, thereby improving both reliability and adaptability.
2Reliability
If monoclonal antibodies are used to treat cancer, then cancer treatments are provided, but cancer incidence and mortality remain high
Solution Approach 1:
The patent extracts the therapeutic action from conventional monoclonal antibodies by developing a novel antibody that specifically targets Claudin-6, a protein selectively expressed on certain cancer cells. This extraction enables more effective tumor targeting and inhibition, directly addressing the high cancer incidence and mortality problem by providing a more reliable treatment mechanism.
Solution Approach 2:
The patent converts the harmful presence of Claudin-6 protein on cancer cell surfaces into a beneficial therapeutic target. By designing an antibody that specifically binds to CLDN6 epitopes, the harmful cancer cell survival mechanism is transformed into a vulnerability that can be exploited for effective tumor inhibition, thereby reducing cancer mortality.
3Ease of operation
If antibody products are designed to recognize and bind to antigens, then specific targeting is achieved, but the ability to inhibit tumor growth without additional moieties is limited
Solution Approach 1:
The patent applies universality by designing an antibody that performs multiple functions through a single molecule: it recognizes and binds to CLDN6 antigens with high specificity, simultaneously mediates tumor growth inhibition, and can induce apoptosis and ADCC effects without requiring additional conjugated moieties. This multi-functionality resolves the contradiction between ease of operation and reliability.
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 antigen-binding proteins effectively inhibit tumor growth and induce tumor regression in CLDN6-expressing cancers, reducing tumor size and preventing recurrence, with high affinity and selectivity for CLDN6 while minimizing side effects.
Implementation Method 1
the antigen-binding protein binds to the extracellular domain (ECD) of CLDN6. In various instances, the antigen-binding protein binds to Extracellular Loop 2 (EL2) of the ECD of CLDN6
Implementation Method 2
inducing apoptosis, ADCC, CDC, or disrupting tumor cell adherence
Implementation Method 3
inducing apoptosis, ADCC, CDC, or disrupting tumor cell adherence
Implementation Method 4
inducing apoptosis, ADCC, CDC, or disrupting tumor cell adherence
Implementation Method 5
disrupting tumor cell adherence
Data Source
AI summary
The present disclosure provides antigen-binding proteins which bind to Claudin-6 (CLDN6). In various aspects, the antigen-binding proteins bind to Extracellular Loop 2 (EL2) of the extracellular domain of CLDN6. Related polypeptides, nucleic acids, vectors, host cells, and conjugates are further provided herein. Kits and pharmaceutical compositions comprising such entities are moreover provided. Also provided are methods of making an antigen-binding protein and methods of treating a subject having cancer.