PMID- 24201868 OWN - NLM STAT- MEDLINE DCOM- 20140813 LR - 20211021 IS - 1476-5500 (Electronic) IS - 0929-1903 (Print) IS - 0929-1903 (Linking) VI - 20 IP - 12 DP - 2013 Dec TI - Highly efficient tumor transduction and antitumor efficacy in experimental human malignant mesothelioma using replicating gibbon ape leukemia virus. PG - 671-7 LID - 10.1038/cgt.2013.67 [doi] AB - Retroviral replicating vectors (RRVs) have been shown to achieve efficient tumor transduction and enhanced therapeutic benefit in a wide variety of cancer models. Here we evaluated two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV), in human malignant mesothelioma cells. In vitro, both RRVs expressing the green fluorescent protein gene efficiently replicated in most mesothelioma cell lines tested, but not in normal mesothelial cells. Notably, in ACC-MESO-1 mesothelioma cells that were not permissive for AMLV-RRV, the GALV-RRV could spread efficiently in culture and in mice with subcutaneous xenografts by in vivo fluorescence imaging. Next, GALV-RRV expressing the cytosine deaminase prodrug activator gene showed efficient killing of ACC-MESO-1 cells in a prodrug 5-fluorocytosine dose-dependent manner, compared with AMLV-RRV. GALV-RRV-mediated prodrug activator gene therapy achieved significant inhibition of subcutaneous ACC-MESO-1 tumor growth in nude mice. Quantitative reverse transcription PCR demonstrated that ACC-MESO-1 cells express higher PiT-1 (GALV receptor) and lower PiT-2 (AMLV receptor) compared with normal mesothelial cells and other mesothelioma cells, presumably accounting for the distinctive finding that GALV-RRV replicates much more robustly than AMLV-RRV in these cells. These data indicate the potential utility of GALV-RRV-mediated prodrug activator gene therapy in the treatment of mesothelioma. FAU - Kubo, S AU - Kubo S AD - Department of Genetics, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Takagi-Kimura, M AU - Takagi-Kimura M AD - Department of Genetics, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Logg, C R AU - Logg CR AD - Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. FAU - Kasahara, N AU - Kasahara N AD - Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. LA - eng GR - P30 DK041301/DK/NIDDK NIH HHS/United States GR - R01 CA121258/CA/NCI NIH HHS/United States GR - P30 DK 41301/DK/NIDDK NIH HHS/United States GR - R01CA121258/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131108 PL - England TA - Cancer Gene Ther JT - Cancer gene therapy JID - 9432230 RN - 0 (Prodrugs) RN - EC 3.5.4.1 (Cytosine Deaminase) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cytosine Deaminase/genetics/metabolism MH - Disease Models, Animal MH - Female MH - Gene Expression MH - Gene Order MH - Genetic Therapy MH - Genetic Vectors/administration & dosage/*genetics MH - Humans MH - Leukemia Virus, Gibbon Ape/*genetics MH - Lung Neoplasms/*genetics/metabolism MH - Mesothelioma/*genetics/metabolism MH - Mesothelioma, Malignant MH - Mice MH - Prodrugs MH - *Transduction, Genetic MH - Virus Replication MH - Xenograft Model Antitumor Assays PMC - PMC8185610 MID - NIHMS1710119 COIS- CONFLICT OF INTEREST CRL and NK are paid consultants to Tocagen Inc. EDAT- 2013/11/10 06:00 MHDA- 2014/08/15 06:00 PMCR- 2021/06/08 CRDT- 2013/11/09 06:00 PHST- 2013/08/25 00:00 [received] PHST- 2013/10/17 00:00 [accepted] PHST- 2013/11/09 06:00 [entrez] PHST- 2013/11/10 06:00 [pubmed] PHST- 2014/08/15 06:00 [medline] PHST- 2021/06/08 00:00 [pmc-release] AID - cgt201367 [pii] AID - 10.1038/cgt.2013.67 [doi] PST - ppublish SO - Cancer Gene Ther. 2013 Dec;20(12):671-7. doi: 10.1038/cgt.2013.67. Epub 2013 Nov 8.