Interaction of measles virus vectors with Auger electron emitting radioisotopes.
A recombinant measles virus (MV) expressing the sodium iodide symporter (NIS) is being considered for therapy of advanced multiple myeloma. Auger electrons selectively damage cells in which the isotope decays. We hypothesized that the Auger electron emitting isotope 125I can be used to control viral proliferation. MV was engineered to express both carcinoembryonic antigen and NIS (MV-NICE). Cells were infected with MV-NICE and exposed to 125I with appropriate controls. MV-NICE replication in vitro is inhibited by the selective uptake of 125I by cells expressing NIS. Auger electron damage is partly mediated by free radicals and abrogated by glutathione. In myeloma xenografts, control of MV-NICE with 125I was not possible under the conditions of the experiment. MV-NICE does not replicate faster in the presence of radiation. Auger electron emitting isotopes effectively stop propagation of MV vectors expressing NIS in vitro. Additional work is necessary to translate these observations in vivo.
Dingli
David
D
Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. dingli.david@mayo.edu
Peng
Kah-Whye
KW
Harvey
Mary E
ME
Vongpunsawad
Sompong
S
Bergert
Elizabeth R
ER
Kyle
Robert A
RA
Cattaneo
Roberto
R
Morris
John C
JC
Russell
Stephen J
SJ
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000235:genetics; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004583:Electrons; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005822:Genetic Vectors / Q000528:radiation effects*; D007457:Iodine Radioisotopes; D008459:Measles virus / Q000235:genetics* / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D027981:Symporters / Q000235:genetics; D014709:Vero Cells; D014779:Virus Replication / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
D000914:Antibodies, Viral; D002272:Carcinoembryonic Antigen; D005609:Free Radicals; D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters