Intraperitoneal therapy of ovarian cancer using an engineered measles virus.
The use of replicating viruses for cancer therapy (virotherapy) holds much promise. We reported previously that the live attenuated Edmonston B vaccine strain of measles virus (MV-Edm) had antineoplastic efficacy against hematological malignancies. In this study, we demonstrate that a recombinant MV-Edm, genetically engineered to express an inert soluble marker peptide (MV-hCEA), is potent against human epithelial ovarian cancer cells in vitro and in vivo. The virus was selectively oncolytic for ovarian tumor cells but caused minimal cytopathic damage on nontransformed ovarian surface epithelium and mesothelium. In contrast to nontransformed cells, the ovarian tumor cells expressed high levels of the measles virus receptor CD46. When injected directly into large established s.c. SKOV3ip.1 human epithelial ovarian xenografts in athymic mice, the virus induced complete regression of 80% of the tumors. i.p. administration of virus enhanced the median survival of mice with advanced i.p. SKOV3ip.1 tumors by >50 days. In addition, we could easily follow the kinetic profile of viral gene expression in the treated mice by determining serum levels of the virally encoded marker peptide (soluble human carcinoembryonic antigen). Trackable recombinant measles viruses warrant further investigation for therapy of ovarian cancer.
Peng
Kah-Whye
KW
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA. peng.kah@mayo.com
TenEyck
Cynthia J
CJ
Galanis
Evanthia
E
Kalli
Kimberly R
KR
Hartmann
Lynn C
LC
Russell
Stephen J
SJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000235:genetics / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology*; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
D015703:Antigens, CD; C497857:CD46 protein, human; D002272:Carcinoembryonic Antigen; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins