Targeting Claudin 18.2 Drug Cell Screening Model

Claudin protein is a type of integrin membrane protein that exists in the tight junction of epithelium and endothelium, which was discovered in 1998 by Shoichiro Tsukita. Tight junctions are the impermeable barriers formed by adjacent cell membranes and are located at the top of polarized epithelial cells and endothelial cells. In addition to Claudin 13, there are 26 Claudin proteins from Claudin 1 to Claudin 27 in humans.

Claudin18 is an important member of the Claudin protein family and a major component of the tight junction between lung and gastric epithelial cells. CLDN18 has two isomers: Claudin 18.1 and Claudin 18.2. In normal tissues, claudin18.1 is only expressed in the lungs, while claudin18.2 is only expressed in limited expression in differentiated epithelial cells on the gastric mucosa. Existing studies have shown that claudin 18.2 is up-regulated in gastric cancer, esophageal cancer, pancreatic cancer and other cancers. When cells become cancerous, the occurrence of malignant tumors will lead to the destruction of tight junctions and make Claudin 18.2 epitopes on the surface of tumor cells. It is exposed and becomes a specific drug target, making this target a research hotspot for molecular targets of anti-tumor drugs. Antibodies targeting claudin 18.2 can bind to the surface of tumor cells to activate ADCC (antibody-dependent cytotoxicity, ADCC) and CDC (complement dependent cytotoxicity, CDC) effects, and at the same time induce cell apoptosis.

Claudin 18.1 and Claudin 18.2 consist of 261 amino acids, four transmembrane domains and two extracellular loops (ECL1, ECL2). Claudin18.1 and Claudin18.2 only have 7 amino acid residue differences in the ECL1 region, making this region an ideal target region for antibody drug design.

The mechanism of the high expression of Claudin 18.2 in tumor cells is not yet very clear. The abnormal expression of Claudin 18.2 may cause structural damage and functional damage of epithelial cells and endothelial cells, and play a role in tumor invasion and metastasis. In addition, studies have shown that the significant changes in the expression level of Claudin 18.2 in cancer cells and normal cells may be due to the high degree of CpG methylation and CpG methylation at the CREB binding site in the Claudin 18.2 promoter region in normal tissues. The level is reduced during tumorigenesis and development, leading to CREB activation and Claudin 18.2 abnormal transcription.

Current status of drugs targeting Claudin 18.2

Claudin 18.2 is a cell membrane surface protein, and the extracellular domain is an ideal target for the development of therapeutic monoclonal antibodies. However, because Claudin 18.1 and Claudin 18.2 have only 7 amino acid residue differences in the extracellular domain ECL1, the design Antibodies that specifically recognize Claudin 18.2 but not Claudin 18.1 have become a challenge for the development of monoclonal antibodies for this target.

At present, the global product types for Claudin 18.2 include monoclonal antibodies, bispecific antibodies, CAR-T and antibody-conjugated ADC drugs. The number of monoclonal antibodies in development is the largest, and Astellas has the fastest progress. IMAB362 (Zolbetuximab, claudiximab) developed. IMAB362 is a human-mouse chimeric antibody that can specifically recognize claudin18.2 protein without binding to any other claudin family members. There are more than 30 targeted Claudin 18.2 drugs under research worldwide, of which only Astellas, Keji Biologics, and Osaican have entered clinical phase II/III trials, and the rest of Claudin 18.2 drugs are in clinical phase I or Earlier development stage.

Targeting Claudin 18.2 Drug Cell Screening Model

In response to the demand for drug development and target research targeting claudin 18.2, we have developed a series of claudin 18.2 drug sieve cell lines. Welcome to inquire.

Part of the product data

Claudin18.2/AGS RQP74131

Claudin18.2/ KATOIII RQP74132

laudin18.2/HGC27 RQP74133