PMID- 30042500 OWN - NLM STAT- MEDLINE DCOM- 20190911 LR - 20200225 IS - 1476-5500 (Electronic) IS - 0929-1903 (Print) IS - 0929-1903 (Linking) VI - 26 IP - 1-2 DP - 2019 Feb TI - Efficient tumor transduction and antitumor efficacy in experimental human osteosarcoma using retroviral replicating vectors. PG - 41-47 LID - 10.1038/s41417-018-0037-y [doi] AB - Retroviral replicating vectors (RRVs) have achieved 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), which utilize different cellular receptors (PiT-2 and PiT-1, respectively) for viral entry, in human osteosarcoma cells. Quantitative RT-PCR showed that low levels of expression of both receptors were observed in normal and non-malignant cells. However, high PiT-2 (for AMLV) and low PiT-1 (for GALV) expression was observed in most osteosarcoma cell lines. Accordingly, AMLV expressing the green fluorescent protein gene infected and replicated more efficiently than GALV in most osteosarcoma cell lines. Furthermore, RRVs expressing the cytosine deaminase prodrug activator gene showed differential cytotoxicity that correlated with the results of viral spread. AMLV-RRV-mediated prodrug activator gene therapy achieved significant inhibition of subcutaneous MG-63 tumor growth over GALV in nude mice. These data indicate that AMLV vectors predominate over GALV in human osteosarcoma cells. Moreover, our findings support the potential utility of the two RRVs in personalized cancer virotherapy on the basis of receptor expression. FAU - Kubo, Shuji AU - Kubo S AD - Unit of Molecular and Genetic Therapeutics, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan. s-kubo@hyo-med.ac.jp. FAU - Takagi-Kimura, Misato AU - Takagi-Kimura M AD - Unit of Molecular and Genetic Therapeutics, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Kasahara, Noriyuki AU - Kasahara N AUID- ORCID: 0000-0002-9186-911X AD - Departments of Cell Biology and Pathology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180725 PL - England TA - Cancer Gene Ther JT - Cancer gene therapy JID - 9432230 RN - 0 (Prodrugs) RN - 0 (Receptors, Virus) RN - 0 (leukemia virus receptor, gibbon ape) RN - EC 3.5.4.1 (Cytosine Deaminase) SB - IM MH - Animals MH - Bone Neoplasms/metabolism/*therapy MH - Cell Line, Tumor MH - Cytosine Deaminase MH - Female MH - Humans MH - *Leukemia Virus, Gibbon Ape MH - *Leukemia Virus, Murine MH - Mice MH - Mice, Nude MH - *Oncolytic Virotherapy MH - Osteosarcoma/metabolism/*therapy MH - Prodrugs MH - *Receptors, Virus MH - Treatment Outcome MH - Xenograft Model Antitumor Assays PMC - PMC6760559 COIS- N.K. is a paid consultant to Tocagen Inc. This does not alter the authors' adherence to all CGT policies on sharing data and materials. The remaining authors declare that they have no conflict of interest. EDAT- 2018/07/26 06:00 MHDA- 2019/09/12 06:00 PMCR- 2018/07/25 CRDT- 2018/07/26 06:00 PHST- 2018/04/01 00:00 [received] PHST- 2018/05/24 00:00 [accepted] PHST- 2018/05/12 00:00 [revised] PHST- 2018/07/26 06:00 [pubmed] PHST- 2019/09/12 06:00 [medline] PHST- 2018/07/26 06:00 [entrez] PHST- 2018/07/25 00:00 [pmc-release] AID - 10.1038/s41417-018-0037-y [pii] AID - 37 [pii] AID - 10.1038/s41417-018-0037-y [doi] PST - ppublish SO - Cancer Gene Ther. 2019 Feb;26(1-2):41-47. doi: 10.1038/s41417-018-0037-y. Epub 2018 Jul 25.