Combination therapy of oncolytic herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft

Int J Cancer. 2015 Apr 1;136(7):1718-30. doi: 10.1002/ijc.29163. Epub 2014 Sep 27.

Abstract

Breast cancer is one of the most common and feared cancers faced by women. The prognosis of patients with advanced or recurrent breast cancer remains poor despite refinements in multimodality therapies involving chemotherapeutic and hormonal agents. Multimodal therapy with more specific and effective strategy is urgently needed. The oncolytic herpes simplex virus (HSV) has potential to become a new effective treatment option because of its broad host range and tumor selective viral distribution. Bevacizumab is a monoclonal antibody against VEGFA, which inhibits angiogenesis and therefore tumor growth. Our approach to enhance the antitumor effect of the oncolytic HSV is to combine oncolytic HSV HF10 and bevacizumab in the treatment of breast cancer. Our results showed that bevacizumab enhanced viral distribution as well as tumor hypoxia and expanded the population of apoptotic cells and therefore induced a synergistic antitumor effect. HF10 is expected to be a promising agent in combination with bevacizumab in the anticancer treatment.

Keywords: HSV; angiogenesis inhibitor; bevacizumab; oncolytic herpes virus HF10.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Bevacizumab
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Cell Proliferation
  • Combined Modality Therapy
  • Cytopathogenic Effect, Viral
  • Female
  • Gene Expression
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics*
  • Humans
  • Mice
  • Oncolytic Virotherapy
  • Oncolytic Viruses / genetics*
  • RNA, Messenger / genetics
  • Simplexvirus / genetics*
  • Tumor Burden
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Virus Replication
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Bevacizumab