Trastuzumab-mediated antibody-dependent cellular cytotoxicity against esophageal squamous cell carcinoma

Area of Science:

• Oncology
• Immunology

Background:

• Esophageal squamous cell carcinoma (SCC) is a significant global health concern.
• HER-2 (Human Epidermal growth factor Receptor 2) is an important therapeutic target in various cancers.
• Understanding HER-2 expression and its role in esophageal SCC is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate HER-2 protein expression and gene amplification in esophageal SCC.
• To evaluate the biological activity of trastuzumab, particularly antibody-dependent cellular cytotoxicity (ADCC), against HER-2-expressing esophageal SCC.
• To assess the correlation between HER-2 expression levels and trastuzumab-mediated ADCC.

Main Methods:

• Ten esophageal SCC cell lines with varying HER-2 statuses were analyzed.
• HER-2 levels were assessed using flow cytometry, immunocytochemistry (HercepTest), and fluorescence in situ hybridization.
• Trastuzumab-induced ADCC, growth inhibition, and apoptosis were evaluated.

Main Results:

• Trastuzumab induced ADCC against HER-2-expressing esophageal SCC, with activity correlating to HER-2 levels determined by flow cytometry.
• Flow cytometry was a more reliable indicator of HER-2 expression for predicting ADCC than HercepTest or FISH.
• Trastuzumab-mediated ADCC was enhanced in SCCs producing transforming growth factor-beta (TGF-β) when co-treated with SB-431542, a TGF-β inhibitor.
• Trastuzumab showed minimal anti-proliferative or apoptosis-inducing effects on HER-2-expressing esophageal SCC.

Conclusions:

• HER-2-expressing esophageal SCC cells are susceptible to trastuzumab-mediated ADCC.
• Flow cytometry is a valuable method for quantifying HER-2 expression to predict trastuzumab response in esophageal SCC.
• Targeting HER-2 with trastuzumab, particularly via ADCC, represents a viable therapeutic strategy for a subset of esophageal SCC patients.