Immunotherapy of HPV infection-caused genital warts using low dose cyclophosphamide

Expert Rev Clin Immunol. 2014 Jun;10(6):791-9. doi: 10.1586/1744666X.2014.907743. Epub 2014 May 12.

Abstract

Condylomata acuminata (CA), caused by human papillomavirus (HPV), is a common sexually transmitted disease with half a million new cases diagnosed in the United States per year and an annual increase in incidence in China. Conventional treatments, including topical cytotoxic agents, surgical excision and physical therapies, are traumatic, cause local side-effects and are invalid for subclinical or latent infection. Exploring immune approaches to eradicate HPV in CA therapeutics are highly desirable. Recent evidence shows that FOXP3(+) regulatory T (Treg) cells are accumulated in genital warts where they mediate immunosuppression. Intriguingly, a low dose of cyclophosphamide (CY), a conventional chemotherapy drug, can selectively target Treg cells, thereby enhancing the function of HPV-specific T cells and NK cells leading to efficient clearance of HPV infection. These findings have important clinical significance, and could potentially lead to a therapeutic breakthrough for the treatment of CA.

Keywords: HPV infection; cyclophosphamide; immunotherapy; regulatory T cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alphapapillomavirus / immunology*
  • China / epidemiology
  • Condylomata Acuminata / drug therapy*
  • Condylomata Acuminata / epidemiology
  • Condylomata Acuminata / immunology
  • Condylomata Acuminata / pathology
  • Cyclophosphamide / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • United States / epidemiology

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide