Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV(Delta51)-NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide symporter gene.
Multiple myeloma is a radiosensitive malignancy that is currently incurable. Here, we generated a novel recombinant vesicular stomatitis virus [VSV(Delta51)-NIS] that has a deletion of methionine 51 in the matrix protein and expresses the human sodium iodide symporter (NIS) gene. VSV(Delta51)-NIS showed specific oncolytic activity against myeloma cell lines and primary myeloma cells and was able to replicate to high titers in myeloma cells in vitro. Iodide uptake assays showed accumulation of radioactive iodide in VSV(Delta51)-NIS-infected myeloma cells that was specific to the function of the NIS transgene. In bg/nd/xid mice with established subcutaneous myeloma tumors, administration of VSV(Delta51)-NIS resulted in high intratumoral virus replication and tumor regression. VSV-associated neurotoxicity was not observed. Intratumoral spread of the infection was monitored noninvasively by serial gamma camera imaging of (123)I-iodide biodistribution. Dosimetry calculations based on these images pointed to the feasibility of combination radiovirotherapy with VSV(Delta51)-NIS plus (131)I. Immunocompetent mice with syngeneic 5TGM1 myeloma tumors (either subcutaneous or orthotopic) showed significant enhancements of tumor regression and survival when VSV(Delta51)-NIS was combined with (131)I. These results show that VSV(Delta51)-NIS is a safe oncolytic agent with significant therapeutic potential in multiple myeloma.
Goel
Apollina
A
Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Carlson
Stephanie K
SK
Classic
Kelly L
KL
Greiner
Suzanne
S
Naik
Shruthi
S
Power
Anthony T
AT
Bell
John C
JC
Russell
Stephen J
SJ
D000818:Animals; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D006801:Humans; D007121:Immunocompetence / Q000276:immunology; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy* / Q000821:virology; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics* / Q000276:immunology; D014779:Virus Replication; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters