Cancer therapy using herpes simplex virus type 1 deficient in the neurovirulence gene ICP34.5, such as the 1716 mutant, has great potential for treating human cancer because intraneoplastic injection of these viruses is able to reduce tumor growth rate and increase survival without toxicity in rodent models of cancer. The overall goal of this proposal is to attempt to further enhance viral therapy by inhibiting the growth of the tumor by preventing angiogenesis concurrent with viral therapy. Towards this goal, the following questions will be addressed: 1) Can the 1716 mutant virus express a functional angiogenesis inhibitor (AI)? An Al expression cassette will replace the latency-associated (LAT) region of 1716, to potentially confer an additional level of safety, and will be analyzed for functional Al expression as well as for a reduced capacity to establish a latent infection and for any potential toxicities associated with Al expression or viral replication. 2) Will this AT-expressing virus be more effective at tumor therapy than the 1716 parental virus? Tumor therapy of an immune-competent, syngenic mouse model of primary and metastatic breast cancer will be examined. 3) What is the mechanism of tumor destruction by the Al-expressing virus? Tumor therapy could be more, less, or equally effective between the two viruses. Angiogenesis inhibition and potential differences in apoptosis or viral replication levels will be examined to decipher the reasons for similarities or differences in viral therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA093034-02
Application #
6515251
Study Section
Special Emphasis Panel (ZRG1-SSS-N (20))
Program Officer
Lohrey, Nancy
Project Start
2002-06-25
Project End
Budget Start
2002-06-25
Budget End
2003-06-24
Support Year
2
Fiscal Year
2002
Total Cost
$44,212
Indirect Cost
Name
University of Pennsylvania
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104