Anticancer oncolytic activity of respiratory syncytial virus

I. Echchgadda, S. Kota, I. Dela Cruz, A. Sabbah, T. Chang, R. Harnack, V. Mgbemena, B. Chatterjee, S. Bose

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Oncolytic virotherapy is an emerging biotherapeutic platform for cancer treatment, which is based on selective infection/killing of cancer cells by viruses. Herein we identify the human respiratory syncytial virus (RSV) as an oncolytic virus. Using prostate cancer models, we show dramatic enhancement of RSV infectivity in vitro in the androgen-independent, highly metastatic PC-3 human prostate cancer cells compared to the non-tumorigenic RWPE-1 human prostate cells. The oncolytic efficiency of RSV was established in vivo using human prostate tumor xenografts in nude mice. Intratumoral and intraperitoneal injections of RSV led to a significant regression of prostate tumors. Furthermore, enhanced viral burden in PC-3 cells led to selective destruction of PC-3 cancer cells in vitro and in xenograft tumors in vivo due to apoptosis triggered by the downregulation of nuclear factor-kB (NF-kB) activity (and the resulting loss of anti-apoptotic function of NF-kB) in RSV-infected PC-3 cells. The intrinsic (mitochondrial) pathway constitutes the major apoptotic pathway; however, the death-receptor-dependent extrinsic pathway, mediated by the paracrine/ autocrine action of tumor necrosis factor-a produced from infected cells, also partly contributed to apoptosis. Thus, the oncolytic property of RSV can potentially be exploited to develop targeted therapeutics for the clinical management of prostate tumors.

Original languageEnglish (US)
Pages (from-to)923-935
Number of pages13
JournalCancer Gene Therapy
Volume16
Issue number12
DOIs
StatePublished - Dec 2009

Keywords

  • Anticancer
  • Apoptosis
  • Oncolytic
  • Prostate cancer
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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  • Cite this

    Echchgadda, I., Kota, S., Dela Cruz, I., Sabbah, A., Chang, T., Harnack, R., Mgbemena, V., Chatterjee, B., & Bose, S. (2009). Anticancer oncolytic activity of respiratory syncytial virus. Cancer Gene Therapy, 16(12), 923-935. https://doi.org/10.1038/cgt.2009.34