Systemic therapy of myeloma xenografts by an attenuated measles virus.
Conditionally replicating viruses are promising agents for the treatment of malignancy. Here it is shown that the live attenuated Edmonston-B vaccine strain of measles virus (MV-Edm) replicates selectively in human myeloma cells and has potent antitumor activity. In vitro, replication of MV-Edm was restricted in phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBLs) but proceeded efficiently in a panel of 6 myeloma cell lines-ARH-77, RPMI 8226, JJN-3, MM1, KAS-6/1, and KMS-11-and in primary myeloma cells isolated by CD138 sorting from the bone marrow aspirates of 6 patients. MV-Edm infection induced potent cytopathic effects in these myeloma cells, resulting in the formation of multinucleated syncytia that eventually became nonviable. In contrast, syncytial formation in PHA-stimulated PBLs was minimal after MV-Edm infection. In vivo, MV-Edm was antitumorigenic and inhibited the establishment of myeloma cells as xenografts in immunocompromised mice. When injected directly into ARH-77 myeloma xenografts in the mice, MV-Edm caused complete regression of these xenografts. MV-Edm administered intravenously into the tail veins of mice also showed significant antineoplastic activity against established RPMI 8226 and ARH-77 xenografts. In particular, the ARH-77 myeloma xenografts were exquisitely sensitive to MV-Edm therapy, and tumors in all mice regressed completely. In light of its selectivity for myeloma cells and its potent antineoplastic activity against myeloma xenografts in vivo, MV-Edm merits further development for the treatment of multiple myeloma.
Peng
K W
KW
Molecular Medicine Program and the Department of Hematology, Mayo Foundation, Rochester, MN 55905, USA.
Ahmann
G J
GJ
Pham
L
L
Greipp
P R
PR
Cattaneo
R
R
Russell
S J
SJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008458:Measles Vaccine / Q000008:administration & dosage; D008459:Measles virus / Q000502:physiology; D051379:Mice; D009101:Multiple Myeloma / Q000628:therapy*; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D014613:Vaccines, Attenuated / Q000008:administration & dosage*; D014779:Virus Replication
D000970:Antineoplastic Agents; D008458:Measles Vaccine; D014613:Vaccines, Attenuated