PMID- 30348946
OWN - NLM
STAT- MEDLINE
DCOM- 20200612
LR  - 20200612
IS  - 1476-5500 (Electronic)
IS  - 0929-1903 (Print)
IS  - 0929-1903 (Linking)
VI  - 26
IP  - 5-6
DP  - 2019 May
TI  - Dual-vector prodrug activator gene therapy using retroviral replicating vectors.
PG  - 128-135
LID - 10.1038/s41417-018-0051-0 [doi]
AB  - Retroviral replicating vectors (RRVs) have been shown to achieve efficient tumor 
      transduction and enhanced therapeutic benefits in a variety of cancer models. In 
      the present study, we evaluated a possible combinatorial effect of prodrug 
      activator genes delivered by two different RRVs derived from amphotropic murine 
      leukemia virus (AMLV) and gibbon ape leukemia virus (GALV) on human 
      hepatocellular carcinoma Hep3B cells. Both RRVs showed efficient replicative 
      spread in culture and can overcame superinfection resistance each other. Notably, 
      the replication and spread of each RRV in culture remained unaffected by 
      pretransduction with the counterpart RRV. We further transduced cells with RRVs 
      which individually possessed the prodrug activator genes yeast cytosine deaminase 
      (CD) and herpes simplex virus thymidine kinase (TK) alone or in combination, and 
      evaluated the cytotoxic effects of RRV-mediated gene therapy with CD and TK in 
      the presence of the respective prodrugs, 5-fluorocytosine and ganciclovir. All 
      combinations of the two prodrug activator genes produced synergistic cytocidal 
      effects, but the combined effects of the different genes were significantly 
      greater than those of the same genes when delivered by two different vectors. The 
      present findings indicate the potential utility of dual-vector gene therapy using 
      two different RRVs carrying different prodrug activator genes.
FAU - Kubo, Shuji
AU  - Kubo S
AD  - Unit of Molecular and Genetic Therapeutics, Laboratory of Medical Innovation, 
      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, Laboratory of Medical Innovation, 
      Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, 
      Japan.
FAU - Tagawa, Masatoshi
AU  - Tagawa M
AD  - Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 
      Chiba, Japan.
FAU - Kasahara, Noriyuki
AU  - Kasahara N
AUID- ORCID: 0000-0002-9186-911X
AD  - Department of Cell Biology and Pathology, University of Miami, Miami, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181022
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Prodrugs)
SB  - IM
MH  - Cell Line, Tumor
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/*genetics
MH  - Humans
MH  - Prodrugs/pharmacology/*therapeutic use
MH  - Retroviridae/*genetics
PMC - PMC6760537
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- 2018/10/24 06:00
MHDA- 2020/06/13 06:00
PMCR- 2018/10/22
CRDT- 2018/10/24 06:00
PHST- 2018/06/13 00:00 [received]
PHST- 2018/09/29 00:00 [accepted]
PHST- 2018/09/24 00:00 [revised]
PHST- 2018/10/24 06:00 [pubmed]
PHST- 2020/06/13 06:00 [medline]
PHST- 2018/10/24 06:00 [entrez]
PHST- 2018/10/22 00:00 [pmc-release]
AID - 10.1038/s41417-018-0051-0 [pii]
AID - 51 [pii]
AID - 10.1038/s41417-018-0051-0 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2019 May;26(5-6):128-135. doi: 10.1038/s41417-018-0051-0. Epub 
      2018 Oct 22.