Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter.
The Edmonston vaccine strain of measles virus (MV-Edm) propagates efficiently in a broad range of human tumor cells, killing them selectively. However, the oncolytic potency of MV-Edm in different human tumor xenograft therapy models is highly variable and there is no convenient way to map the distribution of virus-infected tissues in vivo. To enhance the oncolytic potency of MV-Edm against radiosensitive malignancies and to facilitate noninvasive imaging of infected tissues, we generated a recombinant MV-Edm encoding the human thyroidal iodide symporter (NIS). MV-NIS replicated almost as efficiently as unmodified MV-Edm, and human tumor cells efficiently concentrated radioiodine when infected with MV-NIS. Intratumoral spread of MV-NIS was noninvasively demonstrated by serial gamma-camera imaging of iodine-123 (123I) uptake both in MV-sensitive KAS-6/1 myeloma xenografts, which regressed completely after a single intravenous dose of MV-NIS, and in MM1 myeloma xenografts, which were unresponsive to MVNIS therapy. However, MV-resistant MM1 tumors regressed completely when 131I was administered 9 days after a single intravenous injection of MV-NIS (radiovirotherapy). 131I alone had no effect on MM1 tumor growth. While the potential hematopoietic toxicity of this new therapy requires further evaluation, image-guided radiovirotherapy is a promising new approach to the treatment of multiple myeloma, an incurable but highly radiosensitive plasma cell malignancy. Testing in other radiosensitive cancers is warranted.
Dingli
David
D
Molecular Medicine Program, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Peng
Kah-Whye
KW
Harvey
Mary E
ME
Greipp
Philip R
PR
O'Connor
Michael K
MK
Cattaneo
Roberto
R
Morris
John C
JC
Russell
Stephen J
SJ
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003131:Combined Modality Therapy; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005821:Genetic Techniques; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008459:Measles virus / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000628:therapy*; D009368:Neoplasm Transplantation; D027981:Symporters / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism*; D013997:Time Factors; D014709:Vero Cells; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
D018076:DNA, Complementary; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters