A type of brain tumor that grows from
glial cells. Glial cells make up the
supporting tissue of the brain. Over
half of all brain tumors are gliomas.
Types include astrocytoma,
ependymoma and oligodendroglioma.
Mixed gliomas contain more than one
type of glial cell.

City of Hope researchers plan to
conduct the first-in-human study of a
neural stem cell-based therapy
targeting recurrent high-grade
gliomas, the most aggressive type of
brain tumor.
It was known since 2000 that  neural
stem cells are able  to home in on
invasive tumor cells,  even migrating
from the opposite side of the brain or
across the blood-brain barrier.
The therapy uses a genetically
modified human neural stem cell line,  
to deliver a prodrug-activating enzyme
(cytosine deaminase) to brain tumor
sites. This enzyme converts a relatively
nontoxic prodrug (5-Fluorocytosine, 5-
FC), which is delivered systemically,
into an active cancer-fighting
chemotherapeutic (5-Fluorouracil, 5-
FU). In effect, this stem cell-mediated
strategy achieves production of the
chemotherapeutic drug only in the
area of the tumor. In other words will
work on the  tumor sites while
minimizing exposure to surrounding
healthy tissue. This unique approach
uses  neural stem cells as delivery
vehicles for therapy.
Neural stem cell (NSCs) are the self-
renewing, multipotent cells that
generate the main components of the
nervous system
The clinical trial will begin accepting
patients in the  summer of 2010, with
the goal of enrolling 12 to 20 patients
with recurrent high-grade gliomas. The
modified neural stem cells will be
injected during surgery into the wall of
the cavity remaining after tumor tissue
has been removed. Study patients
then receive daily doses of the
prodrug 5-FC for one week. Based on  
laboratory findings, once the 5-FC
crosses the blood-brain barrier, the
neural stem cells will convert the 5-FC
to the active chemotherapy agent, 5-
FU, at tumor sites in the brain. The
phase I safety trial will assess the
maximum tolerated dose of the therapy.
Prodrugs are a class of drugs, initially
in inactive form, that are converted into
active form in the body by normal
metabolic processes.
Jana Portnow, M.D., assistant
professor and assistant director of the
Brain Tumor Program at City of Hope,
is the principal investigator for the
clinical trial.

The world’s first intra-arterial cerebral
infusion of the drug Avastin direct
inside the malignant brain tumor was
conducted by neurosurgeons at the
NewYork-Presbyterian Hospital/Weill
Cornell Medical Center.
This new  intra-arterial or IA procedure
could render the cancer cells exposed
to increased dosages of the drug
treatment and alongside probably
spare the patient commonly
experienced side effects of being
administered the drug intravenously or
all through the body.
The analytical technique known as
super selective intra-arterial cerebral
Avastin infusion – has shown success
when conducted on 5 patients with
positive outcomes.