title: Replicating retroviral vectors for oncolytic virotherapy of experimental             hepatocellular carcinoma.
abstract: Gene therapy mediated by murine leukemia virus (MLV)-based replicating retrovirus vector (RRV) was previously proven to be highly effective in tumor cell killing, resulting in significant suppression of tumor growth in vivo. Recently, we developed a different form of RRV which is derived from another retrovirus, gibbon ape leukemia virus (GALV), as a cancer therapeutic agent. We compared the gene delivery efficiency and antitumor effects in the two types of RRV in experimental hepatocellular carcinoma (HCC). Our results show that both RRVs can efficiently spread throughout entire HCC cell populations in vitro and achieve high transduction efficiency in HCC xenografts in vivo, while GALV RRV, in general, exhibited more rapid replication kinetics in the tumors. In vitro, substantial HCC cell killing was achieved even when initially only 1% of the HCC cells were producing RRVs that express the yeast cytosine deaminase suicide gene, indicating that the high efficiency of gene transfer by replicative spread of RRVs greatly increased suicide gene toxicity. In vivo, GALV RRV-mediated suicide gene therapy efficiently suppressed HCC tumor growth and no detectable RRV signals were observed in extratumoral tissues, showing promise in using GALV RRV as a cancer therapeutic agent.
authors.affiliation: Division of Hematology-Oncology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan, ROC.
authors.forename: Yin-Che
authors.initials: YC
authors.lastname: Lu
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Yuan-Ren
authors.initials: YR
authors.lastname: Yu
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Lai
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Cheng
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Li
authors.forename: Cheng-Huang
authors.initials: CH
authors.lastname: Shen
authors.forename: Chien-Kuo
authors.initials: CK
authors.lastname: Tai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001711:Biotransformation; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D002470:Cell Survival / Q000187:drug effects; D043525:Cytosine Deaminase / Q000096:biosynthesis / Q000235:genetics; D005437:Flucytosine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D015316:Genetic Therapy; D056945:Hep G2 Cells; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic; D047368:Tumor Burden / Q000187:drug effects; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005656:Fungal Proteins; D011355:Prodrugs; D011994:Recombinant Proteins; D005437:Flucytosine; D043525:Cytosine Deaminase