Expression of immunomodulatory neutrophil-activating protein of Helicobacter pylori enhances the antitumor activity of oncolytic measles virus

Ianko D. Iankov, Cory Allen, Mark J Federspiel, Rae M. Myers, Kah-Whye Peng, James N. Ingle, Stephen J Russell, Evanthia Galanis

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Helicobacter pylori neutrophil-activating protein (NAP) is a major virulence factor and powerful inducer of inflammatory reaction and Th1-polarized immune response. Here, we evaluated the therapeutic efficacy of measles virus (MV) strains engineered to express secretory NAP forms against metastatic breast cancer. Recombinant viruses encoding secretory NAP forms (MV-lambda-NAP and MV-s-NAP) efficiently infect and destroy breast cancer cells by cell-to-cell viral spread and large syncytia formation independently of hormone receptor status. Intrapleural administration of MV-s-NAP doubled the median survival in a pleural effusion xenograft model: 65 days as compared to 29 days in the control group (P < 0.0001). This therapeutic effect correlated with a brisk Th1 type cytokine response in vivo. Secretory NAP was expressed at high levels by infected tumor cells and increased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-12/23 cytokine concentrations were detected in the pleural effusion. In an aggressive model of lung metastatic breast cancer, MV-lambda-NAP and MV-s-NAP also significantly improved survival of the treated animals (P < 0.05) as compared to the control MV strain. These data suggest that potent immunomodulators of bacterial origin, such as H. pylori NAP, can enhance the antitumor effect of oncolytic viruses and support the feasibility and potential of a combined viroimmunotherapy approach.

Original languageEnglish (US)
Pages (from-to)1139-1147
Number of pages9
JournalMolecular Therapy
Volume20
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Oncolytic Viruses
Measles virus
Neutrophils
Proteins
Pleural Effusion
Breast Neoplasms
Cytokines
Interleukin-23
Helicobacter pylori neutrophil-activating protein A
Immunologic Factors
Therapeutic Uses
Virulence Factors
Giant Cells
Interleukin-12
Heterografts
Interleukin-6
Tumor Necrosis Factor-alpha
Hormones
Viruses
Lung

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Expression of immunomodulatory neutrophil-activating protein of Helicobacter pylori enhances the antitumor activity of oncolytic measles virus. / Iankov, Ianko D.; Allen, Cory; Federspiel, Mark J; Myers, Rae M.; Peng, Kah-Whye; Ingle, James N.; Russell, Stephen J; Galanis, Evanthia.

In: Molecular Therapy, Vol. 20, No. 6, 06.2012, p. 1139-1147.

Research output: Contribution to journalArticle

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