Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Line, Tumor
  • Genetic Vectors
  • Green Fluorescent Proteins
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Transplantation, Heterologous
  • Virus Replication

MeSH Major

  • Genetic Therapy
  • Mesothelioma
  • Pleural Neoplasms
  • Simplexvirus

abstract

  • Malignant pleural mesothelioma (MPM) is an aggressive cancer that is refractory to current treatment modalities. Oncolytic herpes simplex viruses (HSV) used for gene therapy are genetically engineered, replication-competent viruses that selectively target tumor cells while sparing normal host tissue. The localized nature, the potential accessibility and the relative lack of distant metastasis make MPM a particularly suitable disease for oncolytic viral therapy. The infectivity, selective replication, vector spread and cytotoxic ability of three oncolytic HSV: G207, NV1020 and NV1066, were tested against eleven pathological types of MPM cell lines including those that are resistant to radiation therapy, gemcitabine or cisplatin. The therapeutic efficacy and the effect on survival of NV1066 were confirmed in a murine MPM model. All three oncolytic HSV were highly effective against all the MPM cell lines tested. Even at very low concentrations of MOI 0.01 (MOI: multiplicity of viral infection, ratio of viral particles per cancer cell), HSV were highly effective against MPM cells that are resistant to radiation, gemcitabine and cisplatin. NV1066, an oncolytic HSV that expresses green fluorescent protein (GFP), was able to delineate the extent of the disease in a murine model of MPM due to selective infection and expression of GFP in tumor cells. Furthermore, NV1066 was able to reduce the tumor burden and prolong survival even when treatment was at an advanced stage of the disease. These findings support the continued investigation of oncolytic HSV as potential therapy for patients with therapy-resistant MPM. Copyright (c) 2006 John Wiley & Sons, Ltd.

publication date

  • May 2006

has subject area

  • Animals
  • Cell Line, Tumor
  • Genetic Therapy
  • Genetic Vectors
  • Green Fluorescent Proteins
  • Humans
  • Male
  • Mesothelioma
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Pleural Neoplasms
  • Simplexvirus
  • Transplantation, Heterologous
  • Virus Replication

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1804293

Digital Object Identifier (DOI)

  • 10.1002/jgm.877

PubMed ID

  • 16475242

Additional Document Info

start page

  • 603

end page

  • 615

volume

  • 8

number

  • 5