TY - JOUR
T1 - Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses
AU - Adusumilli, Prasad S.
AU - Stiles, Brendon M.
AU - Chan, Mei Ki
AU - Mullerad, Michael
AU - Eisenberg, David P.
AU - Ben-Porat, Leah
AU - Huq, Rumana
AU - Rusch, Valerie W.
AU - Fong, Yuman
PY - 2006/5
Y1 - 2006/5
N2 - 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 sup port the continued investigation of oncolytic HSV as potential therapy for patients with therapy-resistant MPM.
AB - 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 sup port the continued investigation of oncolytic HSV as potential therapy for patients with therapy-resistant MPM.
KW - Gene therapy
KW - Herpes simplex virus
KW - NV1066
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U2 - 10.1002/jgm.877
DO - 10.1002/jgm.877
M3 - Article
C2 - 16475242
AN - SCOPUS:33744827944
SN - 1099-498X
VL - 8
SP - 603
EP - 615
JO - Journal of Gene Medicine
JF - Journal of Gene Medicine
IS - 5
ER -