CLDN18
CLDN18 encodes a claudin-family tight-junction protein that localizes at epithelial cell-cell borders and supports barrier structure in lung and stomach tissues[1]. Mechanistically, T/EBP/NKX2.1 regulates CLDN18, and alternative promoter usage generates lung-type CLDN18.1 and stomach-type CLDN18.2 isoforms[1]. In alveolar epithelium, hyperoxia activates the ROS-SPAK-p38 MAPK pathway, suppresses claudin-18, and disrupts tight-junction barrier function[2]. In gastric models, loss of CLDN18 promotes progressive neoplasia, while stomach-type claudin-18 deficiency induces gastritis-linked tumor formation and activates cytokine, stemness, and Wnt signaling networks[3][4]. Compared with lung-specific CLDN18.1, CLDN18.2 is a gastric-lineage isoform retained in gastric and gastroesophageal adenocarcinoma cells and distinguishable by isoform-selective antibodies[5][6]. For experimental and translational applications, zolbetuximab targets CLDN18.2 and improved progression-free and overall survival with chemotherapy in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma trials[6][7][8].
References:
- [1]. Niimi T, et al. claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor, encodes lung- and stomach-specific isoforms through alternative splicing. Mol Cell Biol. 2001 Nov;21(21):7380-90. [Content Brief]
- [2]. Shen CH, et al. SPAK-p38 MAPK signal pathway modulates claudin-18 and barrier function of alveolar epithelium after hyperoxic exposure. BMC Pulm Med. 2021 Feb 15;21(1):58. [Content Brief]
- [3]. Hagen SJ, et al. Loss of Tight Junction Protein Claudin 18 Promotes Progressive Neoplasia Development in Mouse Stomach. Gastroenterology. 2018 Dec;155(6):1852-1867. [Content Brief]
- [4]. Turner JR. Rigor, et al. Rigor, Reproducibility, and Responsibility: A Quantum of Solace. Cell Mol Gastroenterol Hepatol. 2019;7(4):869-871. [Content Brief]
- [5]. Sahin U, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008 Dec 1;14(23):7624-34. [Content Brief]
- [6]. Sahin U, et al. FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann Oncol. 2021 May;32(5):609-619. [Content Brief]
- [7]. Shitara K, et al. 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. Lancet. 2023 May 20;401(10389):1655-1668. [Content Brief]
- [8]. Shah MA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023 Aug;29(8):2133-2141. [Content Brief]
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CLDN18 Related Products (6)
Related Products (6)
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Arcotatug
0 ImagesSynonyms: IBI-343 antibody; HB37A6; TAK-921 AntibodyArcotatug (IBI-343 antibody) is a CLDN18.2 targeting humanized monoclonal antibody. Arcotatug can be used for synthesis of ADCs.
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Emaretamig
0 ImagesCat. No.: HY-P991681CAS No.: 3051701-97-1Synonyms: ASP-2138
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Garetatug
0 ImagesSynonyms: SHR-1904 AntibodyGaretatug is a humanized monoclonal antibody targeting human CLDN18 (claudin-18). Garetatug specifically binds to CLDN18, interfering with relevant cell signaling pathways and exerting antitumor activity.
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ATG-022 Antibody
0 ImagesCat. No.: HY-P992316
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MIL93
0 ImagesCat. No.: HY-P992412MIL93 is a humanized defucosylated IgG1 monoclonal antibody targeting Claudin18.2 (CLDN18.2) with enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. MIL93 can be used for research on advanced solid tumors and gastric cancer. The recommended isotype control is human IgG1 kappa (HY-P99001).
