Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 May 31;10(1):38.
doi: 10.1186/s40364-022-00385-1.

Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy

Weijie Cao #  1 , Haizhou Xing #  1 , Yingmei Li  1 , Wenliang Tian  1 , Yongping Song  2 , Zhongxing Jiang  3 , Jifeng Yu  4
Affiliations
Review

Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy

Weijie Cao et al. Biomark Res. .

Abstract

The claudin18.2 (CLDN18.2) protein, an isoform of claudin18, a member of the tight junction protein family, is a highly selective biomarker with limited expression in normal tissues and often abnormal expression during the occurrence and development of various primary malignant tumors, such as gastric cancer/gastroesophageal junction (GC/GEJ) cancer, breast cancer, colon cancer, liver cancer, head and neck cancer, bronchial cancer and non-small-cell lung cancer. CLDN18.2 participates in the proliferation, differentiation and migration of tumor cells. Recent studies have identified CLDN18.2 expression as a potential specific marker for the diagnosis and treatment of these tumors. With its specific expression pattern, CLDN18.2 has become a unique molecule for targeted therapy in different cancers, especially in GC; for example, agents such as zolbetuximab (claudiximab, IMAB362), a monoclonal antibody (mAb) against CLDN18.2, have been developed. In this review, we outline recent advances in the development of immunotherapy strategies targeting CLDN18.2, including monoclonal antibodies (mAbs), bispecific antibodies (BsAbs), chimeric antigen receptor T (CAR-T) cells redirected to target CLDN18.2, and antibody-drug conjugates (ADCs).

Keywords: Antibody–drug conjugates (ADCs); Bispecific antibody (BsAb); Chimeric antigen receptor T (CAR-T) cells; Claudin18.2; Clinical trial; Immunotherapy; Molecular biomarker; Monoclonal antibody (mAb).

PubMed Disclaimer

Conflict of interest statement

All authors declared no conflicts of interest.

Figures

Fig. 1
Fig. 1
The depiction of Claudin protein structures. Four transmembrane domains (TMDs) with two extracellular loops (ECL), ECL-1 and ECL-2. The ECL-1 contains the highest conserved sequence and the C-CPE C-terminal binds to the ECL-2. Phosphorylation sites locate at the C-terminal of the cytoplasmic site
Fig. 2
Fig. 2
The classification of the TJs and claudins
Fig. 3
Fig. 3
The depiction of genomic organization of the human Claudin18 gene locus on chromosome 3q22, Claudin18.1 and CLaudin18.2 result from alternative splicing of the first exon
Fig. 4
Fig. 4
The crystal structure of the human Claudin4 gives the basic illustration of the Claudins structure, which contains the same main structures for all 27 isoforms of Claudins. 10.1073/pnas.2024651118, https://www.rcsb.org/structure/7kp4
See this image and copyright information in PMC

References

    1. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998;141(7):1539–1550. - PMC - PubMed
    1. Morin PJ. Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res. 2005;65(21):9603–9606. - PubMed
    1. Swisshelm K, Macek R, Kubbies M. Role of claudins in tumorigenesis. Adv Drug Deliv Rev. 2005;57(6):919–928. - PubMed
    1. Resnick MB, Konkin T, Routhier J, Sabo E, Pricolo VE. Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study. Mod Pathol. 2005;18(4):511–518. - PubMed
    1. Sanada Y, Oue N, Mitani Y, Yoshida K, Nakayama H, Yasui W. Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype. J Pathol. 2006;208(5):633–642. - PubMed

LinkOut - more resources