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Drug Target Encyclopedia Series (14) — Claudin 18.2

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Release Time：

2025-12-05 13:55

 

Claudin 18.2 is a tight junction protein selectively expressed in differentiated gastric epithelial cells. Under pathological conditions such as gastric, pancreatic, and esophageal cancers, its restricted expression pattern and stable membrane localization make it an attractive therapeutic target.

Claudin 18.2 is implicated in:

• Gastric adenocarcinoma

• Gastroesophageal junction cancer

• Pancreatic cancer

• Biliary tract cancer

Targeting Claudin 18.2 in therapy:

  • Monoclonal antibodies – Zolbetuximab (anti-CLDN18.2 mAb) has demonstrated efficacy in Claudin 18.2–positive gastric/GEJ cancers and recently received regulatory approval.
  • Antibody-drug conjugates (ADCs) – CLDN18.2-targeted ADCs are advancing in clinical pipelines for solid tumors.
  • Bispecific antibodies – CLDN18.2/CD3 bispecifics redirect T cells to selectively kill CLDN18.2+ tumor cells.
  • CAR-T therapy – CLDN18.2-directed CAR-T therapies are showing promising results in early-phase clinical trials for gastric and pancreatic cancers.

Challenges include:

• Managing on-target, off-tumor toxicity due to low-level expression in normal gastric tissue

• Developing reliable biomarkers to identify CLDN18.2-high patients

• Overcoming tumor heterogeneity and antigen escape

🔬 Ongoing research is focusing on next-generation bispecifics, combination strategies with checkpoint inhibitors, and engineered CAR-T approaches to maximize therapeutic benefit while minimizing toxicity.

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