Cldn18-KO Mouse

Claudin-18 (Cldn18), specifically the isoform Cldn18.2, is a transmembrane protein and a major component of tight junctions, playing a crucial role in maintaining barrier function [4]. It is expressed in normal gastric cells and is retained in malignant gastric or gastroesophageal junction (G/GEJ) adenocarcinoma cells [1].

In recent clinical trials, monoclonal antibodies targeting Cldn18.2 have shown promise. For example, zolbetuximab plus chemotherapy regimens (such as CAPOX or mFOLFOX6) significantly improved progression-free survival and overall survival in patients with Cldn18.2-positive, HER2-negative, locally advanced unresectable or metastatic G/GEJ adenocarcinoma [1,2]. Additionally, Cldn18.2-positive gastric cancer (GC) has distinct immune-microenvironmental characteristics, with differences in the proportion of certain immune cells compared to Cldn18.2-negative tumors [3].

In conclusion, Cldn18.2 is a potential therapeutic target, especially in gastric and gastroesophageal junction adenocarcinomas. The development of monoclonal antibodies against Cldn18.2 offers new treatment options for patients with these malignancies. Understanding the role of Cldn18.2 in the tumor immune microenvironment may also help optimize targeted therapies for these cancers [1,2,3].

References:

1. Shah, Manish A, Shitara, Kohei, Ajani, Jaffer A, Arozullah, Ahsan, Xu, Rui-Hua. 2023. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. In Nature medicine, 29, 2133-2141. doi:10.1038/s41591-023-02465-7. https://pubmed.ncbi.nlm.nih.gov/37524953/

2. Shitara, Kohei, Lordick, Florian, Bang, Yung-Jue, Oh, Mok, Ajani, Jaffer A. 2023. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. In Lancet (London, England), 401, 1655-1668. doi:10.1016/S0140-6736(23)00620-7. https://pubmed.ncbi.nlm.nih.gov/37068504/

3. Jia, Keren, Chen, Yang, Sun, Yu, Zhang, Cheng, Shen, Lin. 2022. Multiplex immunohistochemistry defines the tumor immune microenvironment and immunotherapeutic outcome in CLDN18.2-positive gastric cancer. In BMC medicine, 20, 223. doi:10.1186/s12916-022-02421-1. https://pubmed.ncbi.nlm.nih.gov/35811317/

4. Chen, Jinxia, Xu, Zhiyuan, Hu, Can, Yuan, Li, Cheng, Xiangdong. 2023. Targeting CLDN18.2 in cancers of the gastrointestinal tract: New drugs and new indications. In Frontiers in oncology, 13, 1132319. doi:10.3389/fonc.2023.1132319. https://pubmed.ncbi.nlm.nih.gov/36969060/