Efficacy of Systemically Administered Mutant Vesicular Stomatitis Virus (VSVΔ51) Combined with Radiation for Nasopharyngeal Carcinoma

• Published in: Clinical cancer research 2008-08, Vol.14 (15), p.4891-4897
• Main Authors: ALAJEZ, Nehad M, MOCANU, Joseph D, LO, Kwok-Wai, O'SULLIVAN, Brian, GULLANE, Pat, LIU, Fei-Fei, WEI SHI, CHIA, Marie C, BREITBACH, Caroline J, HUI, Angela B. Y, KNOWLES, Shane, BELL, John C, BUSSON, Pierre, TAKADA, Kenzo
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Apoptosis; Biological and medical sciences; Carcinoma - radiotherapy; Carcinoma - therapy; Cell Line, Tumor; Cell Survival; Combined Modality Therapy - methods; EBV; Humans; Male; Medical sciences; Mice; Mice, Nude; Mutation; Nasopharyngeal Cancer; Nasopharyngeal Neoplasms - radiotherapy; Nasopharyngeal Neoplasms - therapy; Neoplasm Transplantation; Oncolytic virus; Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Radiotherapy; Treatment Outcome; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Vesiculovirus - genetics; Vesiculovirus - metabolism
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-4134

Purpose: Nasopharyngeal carcinoma (NPC) is a malignancy of the head and neck region that is associated with EBV latency. Curative treatments for NPC achieve modest survival rates, underscoring a need to develop novel therapies. We evaluated the therapeutic potential of a mutant vesicular stomatitis virus (VSVΔ51) as single treatment modality or in combination with ionizing radiation (RT) in NPC. Experimental Design: MTS assay was used to assess cell viability in vitro ; apoptosis was measured using propidium iodide staining and caspase activation. In vivo experiments were conducted using tumor-bearing nude mice with or without local RT (4 Gy). Apoptosis was assessed in excised tumor sections with terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling staining. Results: Our data showed that NPC cells are exquisitely sensitive to VSVΔ51 oncolysis, which correlated with the presence of EBV. Efficacy of VSVΔ51 against NPC cells was further augmented when combined with RT. A single systemic injection of VSVΔ51 achieved 50% survival in treated mice, which increased to 83% when combined with local tumor RT. In addition to induction of apoptosis, an antiangiogenic effect of VSVΔ51 was observed in vivo , suggesting a novel tumoricidal mechanism for VSVΔ51. This virus also prevented growth of NPC sphere-forming cells in vitro , showing potential utility in targeting NPC-initiating cells. Conclusions: Our data represent the first report showing that EBV-positive NPC cells are exquisitely sensitive to VSVΔ51 oncolysis and documenting the successful utilization of this combinatorial regimen as a novel curative therapeutic strategy for NPC.