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New targeted treatment for brain tumors shows promise in pre-clinical models
February 15, 2006Monoclonal antibody targets key tumor growth factor; Successfully causes brain tumor regression and improves animal survival
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.
Kennedy Krieger Institute
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.
Kennedy Krieger Institute
Brain Tumor Current Events and Brain Tumor News RSSCancer metabolism discovery uncovers new role of IDH1 gene mutation in brain cancer
Agios Pharmaceuticals today announced that its scientists have established, for the first time, that the mutated IDH1 gene has a novel enzyme activity consistent with a cancer-causing gene, or oncogene.
Barrow study identifies new way to biopsy brain tumors in real time
A new miniature, hand-held microscope may allow more precise removal of brain tumors and an easier recognition of tumor locations during surgery.
Men leave: Separation and divorce far more common when the wife is the patient
A woman is six times more likely to be separated or divorced soon after a diagnosis of cancer or multiple sclerosis than if a man in the relationship is the patient, according to a study that examined the role gender played in so-called "partner abandonment." The study also found that the longer the marriage the more likely it would remain intact.
Childhood cancer survivors less likely to marry, Yale researchers find
Adult survivors of childhood cancer are 20 to 25 percent more likely to never marry compared with siblings and the general population, Yale School of Medicine researchers report in a new study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
Brain tumors in childhood leave a lasting mark on cognition, life status
Brain tumors in childhood cast a long shadow on survivors. The first study of the lasting impact of these tumors -- the most common solid malignancies in childhood -- shows that survivors have ongoing cognitive problems.
Angiochem crosses BBB, shows safety, efficacy in phase 1/2 brain cancer studies
Angiochem, Inc. a clinical-stage biotechnology company developing drugs that are uniquely capable of crossing the blood-brain barrier to treat brain diseases, announced today that its lead drug candidate, ANG1005, has demonstrated a favorable safety and efficacy profile in more than 100 patients with brain cancer from two separate Phase 1 /2 clinical studies in patients with progressive gliomas, including recurrent glioblastoma, and in patients with progressive brain metastases.
Researchers report benefits of new standard treatment study for rare pediatric brain cancer
A team of researchers led by The University of Texas M. D. Anderson Cancer Center unveiled results today from the largest-ever collaborative study addressing the treatment of a rare pediatric brain tumor.
Unequal access: Hispanic children rarely get top-notch care for brain tumors
Hispanic children diagnosed with brain tumors get high-quality treatment at hospitals that specialize in neurosurgery far less often than other children with the same condition, potentially compromising their immediate prognosis and long-term survival, according to research from Johns Hopkins published in October's Pediatrics.
tudy: The new buzz on detecting tinnitus
It's a ringing, a buzzing, a hissing or a clicking - and the patient is the only one who can hear it. Complicating matters, physicians can rarely pinpoint the source of tinnitus, a chronic ringing of the head or ears that can be as quiet as a whisper or as loud as a jackhammer.
New Approach for the Treatment of Malignant Brain Tumors
Initial chemotherapy alone after surgery is just as successful as initial radiation therapy for patients from whom a very malignant brain tumor (anaplastic glioma) was removed. With this treatment, the patients survive on average > 30 months without a recurrence.
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