1. ¹Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
2. ²Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
3. ³South Texas Veterans Health Care System, San Antonio, TX, USA

Correspondence: Dr S Bose, Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC-7758, San Antonio, TX 78229, USA. Tel: +210 567 1019, Fax: +210 567 6612; E-mail: bose@uthscsa.edu; Dr B Chatterjee, Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, USA. E-mail: chatterjee@uthscsa.edu

⁴These authors contributed equally to this work.

Received 3 September 2008; Revised 21 December 2008; Accepted 25 January 2009; Published online 15 May 2009.

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-B (NF-B) activity (and the resulting loss of anti-apoptotic function of NF-B) 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- 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.