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

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).

SUBMITTER: Cao W

PROVIDER: S-EPMC9153115 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Cao Weijie W Xing Haizhou H Li Yingmei Y Tian Wenliang W Song Yongping Y Jiang Zhongxing Z Yu Jifeng J

Biomarker research 20220531 1

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 prol ...[more]

PMID: 35642043

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Project description:Background: Tubulin alpha 1b (TUBA1B) is a key microtubule protein essential for maintaining cellular structure and function. This protein contributes significantly to cytoskeletal formation and is implicated in various diseases. Despite its fundamental roles, TUBA1B's impact on tumor prognosis and the tumor immune microenvironment across cancer types remains inadequately understood. Methods To elucidate TUBA1B's role in cancer prognosis and immune response, we conducted a comprehensive analysis, integrating data from established databases such as The Cancer Genome Atlas, Genotype Tissue Expression, Cancer Cell Lineage Encyclopedia, Human Protein Atlas, Kaplan-Meier Plotter, cBioPortal, TIMER, and ImmuCellAI, along with a large-scale clinical study and immunotherapy cohort. We also conducted in vitro functional assays to assess TUBA1B's functional role in tumor cells, allowing for a detailed examination of its relationship with cancer prognosis and immune modulation. Results: Our findings indicate that TUBA1B expression is dysregulated across multiple cancers, correlating strongly with poor survival outcomes and advanced pathological stages. Functional enrichment analyses further revealed that TUBA1B regulates key cell cycle processes, driving tumor proliferation, migration, and invasion. It also influences immune functions within both the innate and adaptive immune systems, affecting immune-related signaling pathways. These insights underscore TUBA1B's multifaceted role in cancer progression and immune response. Conclusion: This study highlights TUBA1B's potential as a human oncogene with substantial roles in tumorigenesis and immune regulation. Elevated TUBA1B levels are associated with an immunosuppressive tumor microenvironment, impacting cancer progression and treatment outcomes. Targeting TUBA1B may offer promising therapeutic avenues for enhancing cancer treatment, offering new perspectives for innovative anti-tumor strategies with high clinical impact.

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

Publications

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

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