title: Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model.
abstract: OBJECTIVE
  Innovative treatments are needed for metastatic disease involving the pleura. NV1020 is a novel, multimutated, replication-restricted herpes simplex virus under investigation for its ability to selectively kill tumors by means of direct cell lysis. This study examines NV1020 in a rat model of pleura-based lung cancer.
  
  
  METHODS
  Cytotoxicity and viral proliferation were evaluated in vitro by exposure of the human non-small cell lung cancer cell line A549 to virus. NV1020 was also tested in an in vivo pleura-based cancer model established by injecting 1 x 10(7) A549 cells into the thoracic cavity of nude rats. Intrapleural treatments (1 x 10(7) viral particles) were given 3 hours or 3 days after tumor injection to model treatment of microscopic or macroscopic disease (n = 8-9/group). Tumor burden was assessed at 5 weeks. NV1020 infection and dissemination within the thoracic cavity was determined by means of immunohistochemistry.
  
  
  RESULTS
  In vitro, at multiplicities of infection (viral particles per tumor cell) of 0.01, 0.1, and 1.0, cell killing of A549 by NV1020 was 66%, 90%, and 97%, respectively, at 7 days after infection. Viral burst occurred by day 2. Intrapleural treatment was effective for both the microscopic (P <.001) and macroscopic (P <.05) in vivo tumor models. Virus was detectable by means of immunohistochemistry in tumors but not in adjacent normal intrathoracic tissues.
  
  
  CONCLUSIONS
  NV1020 is not only highly cytotoxic to the human lung cancer line A549 in vitro but can be delivered in a clinically relevant fashion to safely and effectively treat pleura-based tumor in vivo in a rat model.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Ebright
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Zager
authors.forename: Sandeep
authors.initials: S
authors.lastname: Malhotra
authors.forename: Keith A
authors.initials: KA
authors.lastname: Delman
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Weigel
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary* / Q000628:therapy*; D000818:Animals; D002460:Cell Line; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation; D010997:Pleural Neoplasms / Q000556:secondary* / Q000628:therapy*; D051381:Rats; D011923:Rats, Nude; D018139:Simplexvirus; D014771:Virion; D014779:Virus Replication