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Synonyms: claudiximab | GC-182 | IMAB-362 | IMAB362
Compound class:
Antibody
Comment: Zolbetuximab (IMAB362) is an investigational, first-in-class monoclonal antibody targeting the cell surface molecule claudin18.2 (CLDN18.2), a pan-cancer drug target [4,8]. Claudin-18 is a tight-junction protein. Splice variant 2 is reported to be a highly selective cell lineage marker of gastric mucosal cells, and it is an active molecular target for tumour-targeted immunotherapy [1-3]. CLDN18.2 is retained on malignant transformation and is expressed in a significant proportion of primary gastric cancers and their metastases, and ectopic expression of CLDN18.2 is identified in distinct histologic subtypes of pancreatic (primary tumour and metastases) [9], esophageal, ovarian, and lung tumours [4]. Zolbetuximab binds to the first extracellular N-terminal domain which is unique to the CLDN18.2 splice variant [4,9].
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| References |
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1. Athauda A, Chau I. (2021)
Claudin 18.2-a FAST-moving target in gastric cancer?. Ann Oncol, 32 (5): 584-586. [PMID:33677015] |
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2. Cao W, Xing H, Li Y, Tian W, Song Y, Jiang Z, Yu J. (2022)
Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy. Biomark Res, 10 (1): 38. [PMID:35642043] |
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3. Kyuno D, Takasawa A, Takasawa K, Ono Y, Aoyama T, Magara K, Nakamori Y, Takemasa I, Osanai M. (2022)
Claudin-18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials. Tissue Barriers, 10 (1): 1967080. [PMID:34486479] |
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4. Sahin U, Koslowski M, Dhaene K, Usener D, Brandenburg G, Seitz G, Huber C, Türeci O. (2008)
Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res, 14 (23): 7624-34. [PMID:19047087] |
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5. Sahin U, Türeci Ö, Manikhas G, Lordick F, Rusyn A, Vynnychenko I, Dudov A, Bazin I, Bondarenko I, Melichar B et al.. (2021)
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, 32 (5): 609-619. [PMID:33610734] |
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6. Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson P, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J et al.. (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. The Lancet, Epub ahead of print. DOI: 10.1016/S0140-6736(23)00620-7 |
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7. Türeci O, Sahin U, Schulze-Bergkamen H, Zvirbule Z, Lordick F, Koeberle D, Thuss-Patience P, Ettrich T, Arnold D, Bassermann F et al.. (2019)
A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus: the MONO study. Ann Oncol, 30 (9): 1487-1495. [PMID:31240302] |
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8. van Laarhoven HWM, Derks S. (2023)
Claudin-18.2 targeting by zolbetuximab: results of SPOTLIGHT in perspective. The Lancet, Epub ahead of print. DOI: 10.1016/S0140-6736(23)00732-8 |
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9. Wöll S, Schlitter AM, Dhaene K, Roller M, Esposito I, Sahin U, Türeci Ö. (2014)
Claudin 18.2 is a target for IMAB362 antibody in pancreatic neoplasms. Int J Cancer, 134 (3): 731-9. [PMID:23900716] |
