BALTIMORE, Feb. 15 /PRNewswire/ -- Gliomas are the most common primary
brain tumors, and also one of the most complicated cancers to treat.
Currently, treatment options such as surgery, radiation and chemotherapy are
only marginally beneficial and present significant risks for patients,
including loss of physical and cognitive abilities. But, a new study
published today in Clinical Cancer Research found that treatment with a novel
monoclonal antibody (mAb) L2G7 inhibited the growth of glioma cells, induced
glioma regression within the brain and prolonged survival -- a finding that
could be translated into human trials as early as next year.
"There is a tremendous need for advancement in the treatment of malignant
brain tumors, which are the number one cancer killer of children under age 20
and a devastating diagnosis for adults as well," said Dr. John Laterra, M.D.,
Ph.D., research scientist at the Kennedy Krieger Institute and senior author
of the study. "The results of this study bring us closer to developing an
alternative treatment option for both adults and for pediatric patients, who
are hardest hit by conventional therapies."
A team of researchers, led by Dr. Jin Kim of Galaxy Biotech, LLC in
Mountain View, CA and Dr. John Laterra of the Kennedy Krieger Institute in
Baltimore, MD, designed the study to evaluate the effectiveness of L2G7 in
treating human gliomas implanted in mouse models. Results indicate that
treatment with L2G7 completely inhibited the growth of the tumors when
established under the skin of animals, while control mAb had only a minimal
effect. Even more promising results were observed in mice with tumors
implanted within the brain. In this setting, L2G7 not only induced tumor
regression, but dramatically increased survival. Animals treated with the
control all died within 41 days of starting the experiment. All mice treated
with L2G7 survived through day 70, and 80% of the animals were alive at day
90, six weeks after stopping the L2G7 treatment.
L2G7 was developed by Dr. Kim's team to inhibit the activities of
hepatocyte growth factor (HGF). HGF is known to be a promising target for
cancer therapy by virtue of its multiple actions that promote cancer
malignancy. HGF stimulates tumor cell division, tumor angiogenesis (blood
vessel formation) and tumor cell resistance to toxic agents such as
chemotherapy and radiation. In this study, brain tumor cells were injected
both under the skin and within the brain to specifically evaluate anti-tumor
responses within the central nervous system. The central nervous system is a
location often protected from cancer therapies by the "blood-brain barrier,"
which could possibly limit the effects of mAb therapy on tumors situated
within the brain. Treatment with L2G7 or a control mAb was given to both
subsets of mice twice weekly.
In one experiment, the researchers delayed treatment of a subset of mice
for 18 days to determine the effect of L2G7 on larger, more advanced tumors
within the brain. At that time, the average tumor size was 26.7 mm3, but
following only three doses of L2G7, tumors shrank to 11.7 mm3. Conversely,
tumors treated with the control mAb grew 5-fold to 134.3 mm3 during the same
period, with a mean volume 12 times larger than the L2G7-treated tumors.
"Monoclonal antibodies to growth factors or their receptors are playing an
increasingly important role in cancer therapy," said Dr. Cary Queen, President
of Galaxy Biotech. "Because of its specificity for HGF, L2G7 may prove to be
particularly effective at halting tumor growth while minimizing side effects
and harm to the surrounding healthy brain cells."
"Our company is committed to the clinical development of L2G7, and we hope
to extend the current success of targeted antibody therapies in the treatment
of breast, colon and lung cancer patients to the treatment of serious central
nervous system malignancies such as gliomas."
In a related study (Lal et al., Clin Cancer Res. 11:4479-4486, 2005), Dr.
Laterra's research team showed that targeting brain tumor HGF with gene
therapy can substantially enhance the anti-tumor effects of radiation therapy,
again emphasizing the important role HGF plays in brain tumors.
About Brain Tumors
Primary brain tumors originate in the brain. As the most common primary
brain tumors, gliomas are the leading cancer killer of children under age 20,
now surpassing acute lymphoblastic leukemia (ALL), and are the third leading
cause of cancer death in young adults ages 20-39, according to the National
Brain Tumor Foundation. Metastatic brain tumors (cancer that spreads from
other parts of the body to the brain) occur at some point in 10-15% of persons
with cancer. Each year, 190,000 people in the United States will be diagnosed
with a primary or metastatic brain tumor. Because brain tumors are located at
the control center for thought, emotion and movement, the effects of toxic
modalities such as chemotherapy and radiation can be devastating, especially
in young children. Surgery to remove malignant brain tumors is a complex and
difficult procedure, and typically does not eliminate all of the cancer cells.
About the Kennedy Krieger Institute
Internationally recognized for improving the lives of children and
adolescents with disorders and injuries of the brain and spinal cord, the
Kennedy Krieger Institute in Baltimore, MD serves more than 12,000 children
each year through inpatient and day treatment programs, outpatient clinics,
home and community services and school-based programs. Kennedy Krieger
provides a wide range of services for children with developmental concerns
mild to severe, and is home to a team of investigators who are contributing to
the understanding of how disorders develop and pioneering new interventions
and earlier diagnosis. For more information on Kennedy Krieger Institute,
About Galaxy Biotech, LLC
A start-up company with laboratories in Mountain View, CA, Galaxy Biotech
is developing humanized antibodies against growth factors and their receptors
for the treatment of cancer. The company was founded by Dr. Jin Kim, who
while a senior scientist at Genentech, Inc. developed the mouse mAb from which
the approved drug Avastin(R) was made, and by Dr. Cary Queen, who previously
co-founded PDL BioPharma, Inc. and developed fundamental technology for the
humanization of antibodies.
SOURCE Kennedy Krieger Institute