SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

V I R A L O N C O L O G Y P R O G R A M
GOALS OF PROGRAM
1) Investigate the regulation of programmed cell
death, membrane transport, interferons,
cytokines, and viral and cellular gene expression
in cancers that arise in immunocompromised
patients.
2) Devise novel therapeutic strategies for therapy
of viral malignancies.
3) Train investigators in the field of viral oncology
and extend our basic and clinical studies
to developing nations with a high incidence of
viral-induced malignancies.
PARTICIPANTS
Barber, Glen N., Ph.D.
Microbiology and Immunology
Boehmer, Paul E., Ph.D.
Biochemistry and Molecular Biology
Boise, Lawrence H., Ph.D.
Microbiology and Immunology
Byrne, Jr., Gerald E., M.D
Pathology
Fontoura, Beatriz M.A., Ph.D.
Molecular and Cellular Pharmacology
Harhaj, Edward W., Ph.D.
Microbiology and Immunology
Harrington, Jr., William J., M.D.
Medicine
Mian, Abdul M., Ph.D.
Medicine
So, Antero G., M.D., Ph.D.
Medicine
HIGHLIGHTS
Basic/Translational Research
• Glen N. Barber, Ph.D., and his colleagues study
the mechanisms of host defense against viral
and malignant disease. Their research focuses
on elucidating the mechanisms of interferons
including their role in regulating apoptosis.
These researchers recently have demonstrated
that vesicular stomatitis virus (VSV), an essentially
nonpathogenic negative-stranded RNA
virus, can selectively induce the cytolysis of numerous
transformed human cell lines in vitro.
The ability of these viruses to selectively kill
tumor cells and not normal cells was dependent
on the protein kinase R/interferon (PKR/IFN)
pathway being defective in susceptible cells.
They have now demonstrated in vivo that tumors
defective in p53 function or transformed
with myc or activated ras also are susceptible to
viral cytolysis, and that the mechanism of viral
oncolytic activity involves the induction of multiple
caspase-dependent apoptotic pathways.
Furthermore, VSV caused significant inhibition
of tumor growth when administered intravenously
in immunocompetent hosts. Their findings
suggest that VSV could be used as a
potential oncolytic agent against a wide variety
of malignant diseases associated with a diversity
of genetic defects. Extensions of this work now
include engineering VSV to express proteins
from viruses associated with cancer such as
hepatitis C (HCV) and human papilloma virus
(HPV) for vaccine and therapeutic purposes.
For example, chimeric VSV containing HCV
structural proteins is being examined as a therapeutic
or preventative vaccine.
• William J. Harrington, Jr., M.D., investigates
the use of antiviral agents in viral-induced malignancies.
He has found that antiviral thymidine
analogues such as azidothymidine (AZT)
and IFN α induce marked apoptosis in Epstein-
Barr virus (EBV) and human herpes virus type
8 (HHV-8)-associated primary effusion lymphomas
(PELs). This therapy was very effective
in eradicating AIDS-related brain lymphoma
and formed the basis for a nationwide clinical
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2004