Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, accounting for most of 18,000 primary brain tumor cases each year in the US. Prognosis is dismal with a median survival of 12-15 mo, despite use of multimodality treatment. Novel therapeutic agents are urgently needed. During the current funding period of the Mayo Brain SPORE, our group was the first to demonstrate that engineered measles virus (MV) strains have significant antitumor activity against gliomas. Their tumor specificity is due to abundant expression of the MV receptor CD46 in glioma cells. The virus upon entry in the tumor cells, causes membrane fusion with neighboring cells, syncytia formation and death. In addition, we have translated this approach into the first human clinical trial of a measles virus derivative producing human carcinoembryonic antigen, MV-CEA (CEA added to facilitate viral monitoring) in recurrent GBM patients. We now hypothesize that by increasing the efficiency and extent of tumor cell destruction and by introducing a therapeutic transgene, we can further augment the antitumor activity of measles virotherapy in gliomas. We propose to accomplish this by testing the translational potential of three novel approaches; a different measles virus strain, MV-NIS, which encodes the sodium iodine symporter (NIS) gene, thus allowing Imaging of viral distribution in vivo; enhancing MV-NIS oncolysis, by exploiting NIS as therapeutic transgene with application of the beta and gamma emitter

Public Health Relevance

Compared to other more common cancers malignant gliomas are responsible for a disproportionate amount of morbidity, in addition to significant decrease in life expectancy. In preclinical models, measles vaccine strains have potent antitumor activity against gliomas and demonstrate synergy with existing therapies. This application proposes to investigate strategies optimizing the use of measles vaccine strains as novel antitumor agents in the treatment of gliomas.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA108961-07
Application #
8555423
Study Section
Special Emphasis Panel (ZCA1-GRB-I (J1))
Project Start
2004-09-20
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
7
Fiscal Year
2012
Total Cost
$201,992
Indirect Cost
$90,423
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Tivnan, Amanda; Heilinger, Tatjana; Ramsey, Joanne M et al. (2017) Anti-GD2-ch14.18/CHO coated nanoparticles mediate glioblastoma (GBM)-specific delivery of the aromatase inhibitor, Letrozole, reducing proliferation, migration and chemoresistance in patient-derived GBM tumor cells. Oncotarget 8:16605-16620
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