Daniel L Price1,2, Pingdong Li1,3, Chun-Hao Chen1, Danni Wong1,3, Zhenkun Yu3, Nanhai G Chen4,5, Yong A Yu4,5, Aladar A Szalay4,5,6, Joseph Cappello4,7, Yuman Fong8, Richard J Wong1. 1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. 2. Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota. 3. Department of Otolaryngology - Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology - Head and Neck Surgery, Ministry of Education, Beijing, China. 4. Genelux Corporation, San Diego Science Center, San Diego, California. 5. Department of Radiation Oncology, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, California. 6. Rudolf Virchow Center for Experimental Biomedicine, Institute for Biochemistry and Institute for Molecular Infection Biology, University of Wurzburg, Am Hubland, Wurzburg, Germany. 7. Protein Polymer Technologies Inc., San Diego, California. 8. Department of Surgery, City of Hope, Duarte, California.
Abstract
BACKGROUND: Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately after surgical resection. METHODS: Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastin-like protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. RESULTS: GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in phosphate-buffered saline (PBS), and at 1 week retains a thousand fold greater infectious plaque-forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and shows increased viral β-galactosidase expression as compared to PBS. CONCLUSION: The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes.
BACKGROUND: Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately after surgical resection. METHODS: Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastin-like protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. RESULTS:GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in phosphate-buffered saline (PBS), and at 1 week retains a thousand fold greater infectious plaque-forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and shows increased viral β-galactosidase expression as compared to PBS. CONCLUSION: The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes.
Authors: J Cappello; J W Crissman; M Crissman; F A Ferrari; G Textor; O Wallis; J R Whitledge; X Zhou; D Burman; L Aukerman; E R Stedronsky Journal: J Control Release Date: 1998-04-30 Impact factor: 9.776
Authors: J Nemunaitis; F Khuri; I Ganly; J Arseneau; M Posner; E Vokes; J Kuhn; T McCarty; S Landers; A Blackburn; L Romel; B Randlev; S Kaye; D Kirn Journal: J Clin Oncol Date: 2001-01-15 Impact factor: 44.544
Authors: Qian Zhang; Yong A Yu; Ena Wang; Nanhai Chen; Robert L Danner; Peter J Munson; Francesco M Marincola; Aladar A Szalay Journal: Cancer Res Date: 2007-10-15 Impact factor: 12.701
Authors: Zhenkun Yu; Sen Li; Peter Brader; Nanhai Chen; Yong A Yu; Qian Zhang; Aladar A Szalay; Yuman Fong; Richard J Wong Journal: Mol Cancer Date: 2009-07-06 Impact factor: 27.401