Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer.
Oncolytic viruses are promising cytoreductive agents for cancer treatment but extensive human testing will be required before they are made commercially available. Here, we investigated the oncolytic potential of two commercially available live attenuated vaccines, Moraten measles and Jeryl-Lynn mumps, in a murine model of intraperitoneal human ovarian cancer and compared their efficacies against a recombinant oncolytic measles virus (MV-CEA) that is being tested in a phase I clinical trial. The common feature of these viruses is that they express hemagglutinin and fusion therapeutic proteins that can induce extensive fusion of the infected cell with its neighbors, resulting in death of the cell monolayer. In vitro, the three viruses caused intercellular fusion in human ovarian cancer cells but with marked differences in fusion kinetics. MV-CEA was the fastest followed by Jeryl-Lynn mumps virus while Moraten measles virus was the slowest, although all viruses eventually caused comparable cell death 6 days postinfection. Tumor-bearing mice treated with 10(6) or 10(7) pfu (one thousand times the vaccine dose) of each of the three viruses responded favorably to therapy with significant prolongations in survival. All three viruses demonstrated equivalent antitumor potency. Commercially available Moraten measles and Jeryl-Lynn mumps vaccines warrant further investigation as potential anticancer agents.
Myers
Rae
R
Toxicology Core, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Greiner
Suzanne
S
Harvey
Mary
M
Soeffker
Diane
D
Frenzke
Marie
M
Abraham
Katalin
K
Shaw
Alan
A
Rozenblatt
Shmuel
S
Federspiel
Mark J
MJ
Russell
Stephen J
SJ
Peng
Kah-Whye
KW
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000235:genetics / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D005260:Female; D006801:Humans; D008458:Measles Vaccine / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009108:Mumps Vaccine / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000628:therapy*; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
D002272:Carcinoembryonic Antigen; D008458:Measles Vaccine; D009108:Mumps Vaccine