SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

C L I N I C A L O N C O L O G Y R E S E A R C H P R O G R A M
such a response despite adequate up-regulation
of costimulatory signal on both transduced and
bystander CLL cells. In addition to being a
highly efficient gene transfer vector, herpes simplex
virus (HSV)-based amplicons possess the
capacity to engage and activate different elements
of the innate immune system. Currently, the
laboratory is studying various aspects of HSV
amplicon/innate immune interaction and how
this might influence the outcome of an adaptive
anti-tumor immune response.
Immune therapeutic strategies targeting the
innate immune system might offer an alternative
pathway to bypass inherent CD8 + T-cell defects,
and effectively mount a systemic anti-tumor immune
response. Dr. Tolba and his colleagues are
currently exploring how HSV amplicon interacts
with the family of toll-like (TL) receptors and
up-regulates NKG2D ligands on target cells.
SELECTED PUBLICATIONS
2002
Tolba, KA, Bowers, WJ, Eling, DJ, Casey, AE,
Kipps, TJ, Federoff, HJ, and Rosenblatt, JD.
Herpes simplex virus (HSV)-amplicon-mediated
delivery of LIGHT enhances the antigen-presenting
capacity of chronic lymphocytic leukemia.
Molecular Therapy 6:455-63, 2002.
Tolba, KA, Bowers, WJ, Muller, J, Housekneckt,
V, Giuliano, RE, Federoff, HJ, and Rosenblatt,
JD. Herpes simplex virus (HSV) amplicon-mediated
codelivery of secondary lymphoid tissue
chemokine and CD40L results in augmented antitumor
activity. Cancer Research 62:6545-51,
2002.
Rosenblatt, JD, Shin, SU, Nechustan, H, Yi,
KH, and Tolba, KA. Potential role of
chemokines in immune therapy of cancer. Israel
Medical Association Journal 4:1054-59, 2002.
VLADIMIR VINCEK, M.D., PH.D.
Associate Professor of Pathology
DESCRIPTION OF RESEARCH
Progress in the understanding of molecular
events involved in the development and progression
of human disease is revolutionizing the
way diseases are diagnosed and treated. Physicians
and scientists now are harnessing the power of
molecular techniques to diagnose and prognosticate
pathologic disorders. Furthermore, it is now
possible to direct therapeutic agents to specific
products expressed by diseased cells without affecting
normal tissues. On the other hand, while
standard histopathologic methods maintain tissue
architecture for morphologic assessment, they do
not preserve macromolecules. The extraction of
nucleic acids from formaldehyde-fixed, paraffinembedded
tissue, the most widely available material
for clinical studies, is a notoriously unreliable
and irreproducible process. Therefore, macromolecules
usually are extracted from fresh or snapfrozen
tissue specimens. Fresh or frozen tissue
specimens, however, are of limited value for the
assessment of histomorphology and cannot be
utilized for long-term retrospective studies. Similarly,
currently available tissue preservatives that
protect nucleic acids cause considerable damage
to the cell and tissue architecture and render
them unsuitable for histomorphologic evaluation.
Current studies in this laboratory show that
it is feasible to simultaneously protect histomorphology
and the integrity of macromolecules in
fixed and processed tissue. The UMFIX reagent,
developed in collaboration with other members
of the Department of Pathology, seems to provide
enormous advantage over the conventional fixation
methods in allowing diagnosis, prognostication,
and identification of treatment targets in
patient samples.
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2004