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Anti-Claudin Treatments in Gastroesophageal Adenocarcinoma: Mainstream and Upcoming Strategies

Giulia Grizzi1, Kostantinos Venetis2,3, Nerina Denaro4

  • 1Operative Unit of Oncology, ASST of Cremona, 26100 Cremona, Italy.

Journal of Clinical Medicine
|April 28, 2023
PubMed

Insights

Claudin 18.2 (CLDN18.2) is a promising target for gastroesophageal adenocarcinoma. Monoclonal antibody zolbetuximab and CAR-T cells show potential in treating CLDN18.2-positive GEAC, with zolbetuximab improving patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunotherapy

Background:

  • Claudins (CLDNs) are key tight junction proteins regulating cell adhesion and permeability.
  • Downregulation of CLDNs promotes malignant cell growth and epithelial transition.
  • Claudin 18.2 (CLDN18.2) is highly expressed in advanced gastroesophageal adenocarcinoma (GEAC), making it a therapeutic target.

Purpose of the Study:

  • To review novel therapeutic strategies for CLDN18.2-positive GEAC.
  • To focus on the efficacy of zolbetuximab, an anti-CLDN18.2 monoclonal antibody.
  • To discuss the application of engineered anti-CLDN18.2 chimeric antigen receptor (CAR)-T cells.

Main Methods:

  • Review of preclinical and clinical data on CLDN18.2 targeted therapies.
  • Analysis of results from Phase II and III trials of zolbetuximab.
  • Evaluation of safety and efficacy data for anti-CLDN18.2 CAR-T cells.

Main Results:

  • Zolbetuximab demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to standard chemotherapy in the SPOTLIGHT trial.
  • CLDN18.2 aberrations are prevalent in a significant subset of metastatic GEAC cases.
  • Anti-CLDN18.2 CAR-T cells have shown preliminary efficacy but are associated with hematologic toxicities.

Conclusions:

  • Zolbetuximab represents a significant advancement in treating CLDN18.2-positive GEAC.
  • Engineered CAR-T cells offer a potential alternative immunotherapy approach for CLDN18.2-positive GEAC.
  • Targeting CLDN18.2 is a validated strategy for advanced GEAC treatment.
Keywords:
anti-claudin 18.2car-T cellschemotherapyclaudinsesophageal cancergastric cancerzolbetuximab

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