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Imaging and therapy of malignant pleural mesothelioma using replication‐competent herpes simplex viruses
Author(s) -
Adusumilli Prasad S.,
Stiles Brendon M.,
Chan MeiKi,
Mullerad Michael,
Eisenberg David P.,
BenPorat Leah,
Huq Rumana,
Rusch Valerie W.,
Fong Yuman
Publication year - 2006
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.877
Subject(s) - oncolytic virus , herpes simplex virus , multiplicity of infection , cancer research , oncolytic adenovirus , genetic enhancement , virology , cell culture , radiation therapy , mesothelioma , medicine , biology , virus , pathology , gene , biochemistry , genetics
Background 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. Methods 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. Results 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. Conclusion These findings support the continued investigation of oncolytic HSV as potential therapy for patients with therapy‐resistant MPM. Copyright © 2006 John Wiley & Sons, Ltd.