Recombinant interleukin-2 enhanced the antitumor effect of ADV/RSV-HSV-tk/ACV therapy in a murine bladder cancer model.
BACKGROUND
Previous studies demonstrated the antitumor effects of IL-2 and ADV/RSV-HSV-tk in bladder tumor models. In our study, we employed the intramuscular injection of recombinant IL-2 combined with ADV/RSV-HSV-tk gene therapy in the MBT-2 murine bladder tumor model.


METHODS
In the in vitro study, after adenoviral gene transduction efficiency had been assessed, the cytotoxicity of ADV/RSV-HSV-tk/ACV was examined. In the in vivo study, ADV/RSV-HSV-tk was injected into MBT-2 subcutaneous tumors, ACV was injected intraperitoneally daily for 13 days and recombinant IL-2 was injected intramuscularly daily for 10 days.


RESULTS
The X-gal staining of MBT-2 cells infected with 125 multiplicity of injection (MOI) indicated > 20% adenoviral gene transduction efficiency. The cell growth of MBT-2 infected with 125 MOI was significantly inhibited by 40 microM of ACV. In the in vivo study, the combination therapy significantly inhibited tumor growth in the MBT-2 tumor model.


CONCLUSIONS
The systemic administration of recombinant IL-2 in combination with HSV-tk gene therapy exhibited an enhanced antitumor effect.
Terao
Shuji
S
International Center for Medical Research and Treatment, Kobe University School of Medicine, Japan. terao@med.kobe-u.ac.jp
Shirakawa
Toshiro
T
Goda
Kazumasa
K
Kamidono
Sadao
S
Fujisawa
Masato
M
Gotoh
Akinobu
A
D000212:Acyclovir / Q000493:pharmacokinetics / Q000494:pharmacology*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004357:Drug Synergism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000494:pharmacology; D018139:Simplexvirus / Q000201:enzymology / Q000254:growth & development; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy*
D007376:Interleukin-2; D011994:Recombinant Proteins; D013937:Thymidine Kinase; D000212:Acyclovir