CLDN18.2 Antibody-Drug Conjugate with Self-Immolative Linker
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current chemotherapeutic agents for cancer treatment often cause systemic toxicity and side effects due to non-specific delivery, and there is a need for targeted therapies that can selectively target cancer cells while minimizing harm to healthy tissues.
Innovation Solution
Development of an antibody-drug conjugate (ADC) specifically targeting claudin 18 isoform 2 (CLDN18.2) using a novel antibody and a linker with a self-immolative group that is stable in plasma and body circulation, allowing for controlled release of the drug within cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional chemotherapeutic agents are administered systemically, then cancer treatment coverage is achieved, but systemic toxicity and side effects increase
Solution Approach 1:
The chemotherapeutic agent is segmented and attached specifically to the antibody molecule, creating a targeted delivery system where the drug is confined to the antibody's circulation path and only released at the target tumor site, rather than being distributed systemically throughout the body
Solution Approach 2:
The antibody serves as an intermediary carrier that bridges the gap between the chemotherapeutic agent and the target cancer cells. The antibody binds to CLDN18.2 on tumor cell surfaces, delivering the attached drug specifically to cancer cells while avoiding healthy tissues
2Object-affected harmful factors
If targeted delivery to cancer cells is achieved, then toxicity is reduced, but drug release control becomes critical
Solution Approach 1:
The linker's chemical stability parameters are optimized to remain stable in the circulation environment (resisting hydrolysis and enzymatic degradation) but undergo parameter change upon reaching the intracellular environment, where pH and enzymatic conditions trigger controlled drug release
Solution Approach 2:
The linker contains a self-immolative group that automatically triggers drug release through intracellular enzymatic hydrolysis without requiring external intervention. The system serves itself by using the intracellular environment's own conditions (enzymes, pH) to activate drug release
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 ADC effectively delivers the drug to cancer cells, maximizing efficacy while reducing systemic toxicity and side effects by ensuring the drug is released only in target cells, thereby enhancing treatment specificity and safety.
Implementation Method 1
the linker needs to not only play a functional role in linking the antibody and the drug, but also ensure that the drug is released properly through antibody-drug dissociation (e.g., as a result of hydrolysis by an enzyme) after being circulated through the body
Data Source
AI summary
The present disclosure relates to a novel antibody-drug conjugate (ADC) targeting claudin 18 isoform 2 (CLDN18.2), an active metabolite of the ADC, a method of producing the ADC, use of the ADC for the treatment and/or prevention of diseases, and use of the ADC for producing a drug for the treatment and/or prevention of diseases, more specifically hyperproliferative and/or angiogenic diseases, for example, cancer, and more particularly, to an antibody-drug conjugate including a novel antibody or antigen-binding fragment thereof that binds to CLDN18.2, and a pharmaceutical composition including the same.