In vitro cytotoxic effect of Trastuzumab in combination with Pertuzumab in breast cancer cells is improved by interleukin-2 activated NK cells

Mol Biol Rep. 2019 Dec;46(6):6205-6213. doi: 10.1007/s11033-019-05059-0. Epub 2019 Sep 6.

Abstract

Targeting erb-b2 receptor tyrosine kinase 2 (ERBB2) using the combination of Trastuzumab and Pertuzumab has demonstrated promising results in breast cancer therapy. It has further been revealed that interleukin-2 (IL-2) can activate Natural Killer cells (NK cells) and elevate their cytotoxic potency against tumor cells. In this study, we explored the cytotoxic effect of recombinant human IL-2 in combination with Trastuzumab and Pertuzumab on the ERBB2 positive (SK-BR-3) and negative (MDA-MB-231) breast cancer cell lines. The cytotoxicity level of IL-2 activated NK cells (approximately 75%) were significantly higher than untreated cells (approximately 55%) in the presence of Trastuzumab and Pertuzumab against SK-BR-3 cells, while no difference was observed in the case of MDA-MB-231 cells (about 15%).

Keywords: Breast cancer; Immunotherapy; Interleukin 2; Pertuzumab; Trastuzumab.

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antineoplastic Agents, Immunological / pharmacology
  • Biomarkers
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cytokine-Induced Killer Cells / drug effects*
  • Cytokine-Induced Killer Cells / immunology*
  • Cytokine-Induced Killer Cells / metabolism
  • Drug Synergism
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / pharmacology*
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Trastuzumab / pharmacology*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Biomarkers
  • Interleukin-2
  • pertuzumab
  • Trastuzumab