Mechanism of action of the trastuzumab biosimilar CT-P6

Expert Opin Biol Ther. 2019 Oct;19(10):1085-1095. doi: 10.1080/14712598.2019.1554052. Epub 2018 Dec 13.

Abstract

Objectives: Therapeutic monoclonal antibody biosimilars are expected to help reduce the sizeable economic burden of targeted treatments. Trastuzumab (Herceptin®), a recombinant humanized monoclonal antibody that binds to the extracellular domain of HER2, is approved for use in HER2-overexpressing breast cancer (in both the adjuvant and metastatic settings) and HER2-positive gastric cancer. CT-P6 (Herzuma®) is a biosimilar of trastuzumab, designed to bind with high affinity and specificity to the same HER2 epitope as the reference product. We investigated whether CT-P6 exerts its effects through the same mechanism of action as trastuzumab. Methods: The mechanism of action of CT-P6 and trastuzumab, both as monotherapy and in combination with paclitaxel or pertuzumab, was compared in HER2-overexpressing breast cancer and gastric cancer cell models. Results: We confirmed that CT-P6 functions in a manner similar to trastuzumab by binding to the HER2 receptor, which is central to the effects of trastuzumab in all indications. Conclusions: Collectively, the results of this study show that the mechanisms of action of CT-P6 and trastuzumab are similar in HER2-positive breast cancer and gastric cancer models and, therefore, CT-P6 can be expected to perform similarly in the clinical setting.

Keywords: Biosimilar; CT-P6; breast cancer; gastric cancer; mechanism of action; trastuzumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Biosimilar Pharmaceuticals / chemistry
  • Biosimilar Pharmaceuticals / metabolism*
  • Biosimilar Pharmaceuticals / pharmacology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Female
  • Humans
  • Paclitaxel / pharmacology
  • Phagocytosis / drug effects
  • Phosphorylation
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction / drug effects
  • Trastuzumab / chemistry
  • Trastuzumab / metabolism*
  • Trastuzumab / pharmacology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Phytogenic
  • Biosimilar Pharmaceuticals
  • CT-P6
  • Vascular Endothelial Growth Factor A
  • Receptor, ErbB-2
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • pertuzumab
  • Trastuzumab
  • Paclitaxel