Authors:

Hayley Alderson¹, Katie Lefley¹, Lesly Fregoso¹, Achintya Bharadwaj¹, Dan Castellanos-McKenney¹, Siena Tabuena-Frolli¹, Donna Kell¹, Xinlai Yao², Xueming Qian², Li Xu³, Caroline Germa³, Emin Oroudjev¹

¹Agilent Technologies, Inc. ²Suzhou Transcenta Therapeutics Co., Limited ³Transcenta Therapeutics Inc

Introduction:

Claudin-18 isoform 2 (Claudin 18.2) belongs to the human claudin family of tetraspan membrane proteins that are crucial structural and functional components of tight junctions. Unlike other family members, Claudin 18.2 is a tissue-restricted marker that is expressed only in differentiated epithelial cells of the gastric mucosa. In cancer, Claudin 18.2 is ectopically expressed at a significant level in multiple tumor types.Claudin 18.2 acts as a cell membrane surface protein with an exposed extracellular structure allowing antibody binding and it is suggested that Claudin 18.2 can be an ideal target for the development of therapeutic monoclonal antibodies.

A mouse anti-Claudin 18.2 monoclonal antibody, clone 14G11, was developed by Transcenta. The antibody was generated against a linear epitope located on the extracellular domain of loop1 and has a binding site that overlaps with the binding site of therapeutic antibody Osemitamab. It was selected by Transcenta to develop an IHC assay in collaboration with Agilent Technologies, Inc.

Agilent Technologies, Inc. is developing Claudin 18.2 IHC 14G11 pharmDx as an immunohistochemical (IHC) assay for the detection of Claudin 18.2 protein in gastric and gastroesophageal junction (GEJ) adenocarcinoma in support of clinical studies conducted by Transcenta Therapeutics.

Conclusions:

Analytical verification testing indicates Claudin 18.2 IHC 14G11 pharmDx is a sensitive, specific, precise, and robust assay for detecting Claudin 18.2 in gastric and GEJ adenocarcinoma. Claudin 18.2 IHC 14G11 pharmDx for Investigational Use Only/for Performance Evaluation Only will be used for patient selection in the phase III trial of gastric/GEJ adenocarcinoma where applicable ethics committee and regulatory approvals have been granted.