Noninvasive imaging and radiovirotherapy of prostate cancer using an oncolytic measles virus expressing the sodium iodide symporter.
Prostate cancer cells overexpress the measles virus (MV) receptor CD46. Herein, we evaluated the antitumor activity of an oncolytic derivative of the MV Edmonston (MV-Edm) vaccine strain engineered to express the human sodium iodide symporter (NIS; MV-NIS virus). MV-NIS showed significant cytopathic effect (CPE) against prostate cancer cell lines in vitro. Infected cells effectively concentrated radioiodide isotopes as measured in vitro by Iodide-125 ((125)I) uptake assays. Virus localization and spread in vivo could be effectively followed by imaging of (123)I uptake. In vivo administration of MV-NIS either locally or systemically (total dose of 9 x 10(6) TCID(50)) resulted in significant tumor regression (P < 0.05) and prolongation of survival (P < 0.01). Administration of (131)I further enhanced the antitumor effect of MV-NIS virotherapy (P < 0.05). In conclusion, MV-NIS is an oncolytic vector with significant antitumor activity against prostate cancer, which can be further enhanced by (131)I administration. The NIS transgene allows viral localization and monitoring by noninvasive imaging which can facilitate dose optimization in a clinical setting.
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Pavlos
P
Msaouel
Ianko D
ID
Iankov
Cory
C
Allen
Ileana
I
Aderca
Mark J
MJ
Federspiel
Donald J
DJ
Tindall
John C
JC
Morris
Michael
M
Koutsilieris
Stephen J
SJ
Russell
Evanthia
E
Galanis
D000818:Animals; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D003952:Diagnostic Imaging; D005818:Genetic Engineering; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D008458:Measles Vaccine / Q000235:genetics*; D008459:Measles virus / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014709:Vero Cells; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D008458:Measles Vaccine; D027981:Symporters; D000099209:Sodium-Iodide Symporters