Brain Tumor and Neuro-Oncology Center - Cleveland Clinic

2008 ANNUAL REPORT
BTNC Laboratory Research/Innovations
Basic Research Research at Cleveland Clinic continues
to grow and prosper through recruitment of outstanding
new staff, improvement and expansion of facilities,
development of extensive infrastructure and support
services, and enhancement of education programs.
Central to the success of the BTNC is advancing
the care of brain tumor patients through better
understanding of the causes and mechanisms of tumor
development. Basic science research efforts are focused
on identifying the genetic, cellular and molecular biology
of malignant and benign brain tumors; investigating
the mechanism of tumor formation; and exploring new
therapeutic developments for brain tumor treatments.
Below are examples of projects being conducted in the
basic research labs.
• Development of immunotherapy for malignant glioma
using vaccines formed by fusing tumor cells with
dendritic cells (Dr. Gregory Plautz)
• Characterization of the tumor antigen profile of
brain tumor stem cells to determine whether there
are common glioma antigens, which would make
it possible to develop a standardized glioma vaccine
(Dr. Gregory Plautz)
• The ability of dendritic cell/tumor cell fusion vaccines
and adoptive transfer of tumor-sensitized T cells to
cure established brain tumors, being tested in mouse
models as a prelude to future clinical trials (Dr.
Gregory Plautz)
• Investigations into alterations in DNA repair
mechanisms that may improve the chemo- and
radio-sensitivity of malignant gliomas (Dr. Michael
Vogelbaum)
• Examination of the role of NFkappaB and IL-8 in
driving the invasion of malignant gliomas (Dr.
Michael Vogelbaum and Dr. Baisakhi Raychaudhuri)
• Production of tumor-specific toxicity in malignant
gliomas by modified small interfering RNA molecules
(Dr. Michael Vogelbaum and Dr. Jose Valerio)
• Development of a novel assay for MGMT function
(Dr. Michael Vogelbaum and Dr. Cliff Robinson)
BTNC Primary Laboratories
Center for Translational Therapeutics –
Vogelbaum Laboratory
The BTNC’s Center for Translational Therapeutics,
directed by Dr. Michael A. Vogelbaum, performs preclinical
testing of the most promising anti-cancer agents
that may be of use for treating malignant brain tumors.
One goal of the Center for Translational Therapeutics
is to accelerate the lengthy and expensive process of
testing new drugs targeted against brain tumors and to
safely move these drugs into clinical trials as quickly as
possible for the benefit of patients.
Physicians, researchers and scientists involved in
this center work with pharmaceutical companies and
other medical institutions to identify, obtain and test
new compounds. The center’s efforts, including an
international search for all potential brain tumor-relevant
therapies, have yielded several promising agents for
testing. Testing of new agents involves evaluating
the toxicity and efficacy of these compounds in the
laboratory and in animals that have brain tumors.
In addition, we are investigating the optimal route of
delivery of these drugs.
Because many new therapeutic agents cannot penetrate
the central nervous system, center researchers are
exploring alternative delivery methods. In addition to
investigating the efficacy of oral delivery, researchers
evaluate the efficacy of the agents when delivered
intracerebrally – directly into the brain – via a
specialized neurosurgical technique called convectionenhanced
delivery (CED). Furthermore, in collaboration
with investigators in the Department of Biomedical
Engineering of Lerner Research Institute (LRI),
we are evaluating alternative formulations using
nanotechnology, which may enhance distribution of
potential therapeutics within the brain.
The center has started research projects with a number
of pharmaceutical and biotechnology companies ranging
in size from small startup firms to some of the largest
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