Effects of a human compact anti-ErbB2 antibody on gastric cancer

Gastric Cancer. 2014 Jan;17(1):107-15. doi: 10.1007/s10120-013-0244-z. Epub 2013 Mar 5.

Abstract

Background: Gastric cancer represents one of the most common causes of cancer deaths worldwide. Overexpression of ErbB2, a tyrosine kinase receptor involved in the pathogenesis of several human cancer types, has been reported also in gastric cancer. Thus, the inhibition of ErbB2 signal transduction pathways by the use of human antibodies could be a valuable strategy for the therapy of this type of cancer.

Methods: We tested for the first time the antitumor effects on gastric cancer cells of Erb-hcAb, a novel fully human compact antibody, prepared in our laboratory, which targets a different epitope of ErbB2 with respect to trastuzumab, the only anti-ErbB2 antibody currently in clinical use for both breast and gastric cancer therapy.

Results: Herein we demonstrate that the in vitro and in vivo growth of gastric cancer cells is efficiently inhibited by Erb-hcAb, which shows antitumor effects on the NCI-N87 cell line more potent than those observed for trastuzumab.

Conclusions: Erb-hcAb could be a promising candidate in the immunotherapy of gastric cancer as it combines the antiproliferative effect associated with the inhibition of ErbB2 signaling on tumor target cells with the ability to induce antibody-dependent cellular cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Immunoconjugates / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Targeted Therapy / methods*
  • Receptor, ErbB-2 / immunology*
  • Receptor, ErbB-2 / metabolism*
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Trastuzumab
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Erb-hcAb
  • Immunoconjugates
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab