Encouraging Data Presented on Oncophage(R) Vaccine at International Conference

Antigenics (NASDAQ: AGEN) today announced that data from a multi-center Phase 1/2 clinical trial of Oncophage (vitespen) for recurrent high-grade glioma (brain cancer) was presented at the International Conference on Brain Tumor Research and Therapy. The study was conducted by the Brain Tumor Research Center at the University of California, San Francisco (UCSF).

Data from 32 evaluable patients suggest that vaccination with Oncophage may improve overall survival in patients with recurrent high-grade glioma. An overall median survival of 44 weeks after tumor resection was observed. Approximately 70% of the evaluable patients survived beyond 36 weeks, and 41% survived up to or longer than one year. This is considered a significant achievement in the treatment of recurrent high-grade glioma. In addition, Oncophage was well tolerated, with no serious adverse events attributable to the vaccine.

Glioblastoma, the brain tumor that killed Senator Ted Kennedy, still mostly untreatable, say docs Read more: http://www.nydailynews.com/lifestyle/hea

BY Rosemary Black
DAILY NEWS STAFF WRITER

Tuesday, September 1st 2009, 11:00 AM

Ted Kennedy waged a battle against one of the most lethal of all brain tumors -- and at first, as the Massachusetts senator kept active seeing friends and going on his beloved sailboat, he almost seemed to have the upper hand.

But despite his access to the best medical treatment available, Kennedy lost the fight of his life just 15 months after his diagnosis.

Kennedy and others unlucky enough to learn they have glioblastoma receive a grim prognosis: about a year or a little more is the average life expectancy.

The outlook hasn’t changed all that much in the last 40 years, according to Dr. Eugene S. Flamm, chairman of neurosurgery at Montefiore Medical Center.

“It is a rapidly growing tumor that does not respond to treatment,” he says. “Even if you remove it surgically, the outcome is the same. The transformation of normal brain cells into tumor cells continues even after surgery.”

Despite the gloomy outlook, some doctors are more optimistic.

“It depends how you measure success,” says Dr. Alan Hirschfeld, chairman of neurosurgery at St. Vincent’s Hospital Manhattan. “If you measure it by extending life for two or three months, it’s successful. If you measure it in terms of curing the patient, no, we haven’t succeeded.”

“Survival time has increased very definitely,” says Dr. Michael Gruber, an oncologist at NYU Langone Medical Center. “How well a patient does depends on four indicators. Age is one. If you are over 50, your prognosis is worse than someone who is under 50. It also depends on the grade of tumor, whether it can be taken out, and a patient’s neurological status.”

In 2005, a drug called temozolomide was added to radiation therapy as the treatment for this type of tumor, and the median survival time was 14.6 months, according to the New York Times. Temozoliomide, which is taken orally and has fewer side effect than older drugs that were given intravenously, is now the go-to drug for treating glioblastoma.

Unfortunately, this rapidly growing tumor is virtually impossible to completely remove, says Hirschfeld.

“Although you can see something that looks very well defined on the MRI, the tumor extends well beyond those borders,” he says. “Even if you get 99.9 percent of it, you could still be left with 10 million cells that can grow and cause a recurrence.”

The cost of treating such a brain tumor is high -- from $100,000 to $500,000 is the figure experts at various medical centers tossed out, according to the New York Times.

When Kennedy was undergoing treatment, his own doctors couldn’t agree on whether he should have surgery, the Times reported. The senator flew to Duke for a three-plus hours operation in June that his doctors billed as “successful." But he lived just a few months longer.

Though there are no known risk factors for this type of tumor, it seems to strike people between the ages of 50 and 70 the most frequently, says Hirschfeld. It’s about equally common in men and women.

While new findings continue to extend the lives of patients with glioblastoma, for the moment, it remains one of the most dreaded diagnoses. For those who receive it, putting up a fight against the tumor may help.

“If you go to the Internet and do a search on outcomes in glioma, everyone will call it a terminal illness,” Dr. Henry Friedman, co-director of Duke’s brain tumor center, told the Times. “Your outcome is ‘dead on diagnosis.’ If you don’t have the philosophy that you can win, you have lost before you started.”

Salk researchers develop novel glioblastoma mouse model

La Jolla, CA th Researchers at the Salk Institute for Biological Studies have developed a versatile mouse model of glioblastoma-the most common and deadly brain cancer in humans-that closely resembles the development and progression of human brain tumors that arise naturally.

(Media-Newswire.com) - La Jolla, CA – Researchers at the Salk Institute for Biological Studies have developed a versatile mouse model of glioblastoma—the most common and deadly brain cancer in humans—that closely resembles the development and progression of human brain tumors that arise naturally. "Mouse models of human cancer have taught us a great deal about the basic principles of cancer biology," says Inder Verma, Ph.D., a professor in the Laboratory of Genetics. "By definition, however, they are just that: approximations that simulate a disease but never fully capture the molecular complexity underlying disease in humans." Trying to mimic randomly occurring mutations that lie at the heart of all tumors, the Salk researchers used modified viruses to shuttle cancer-causing oncogenes into a handful of cells in adult mice. Their strategy, described in the Jan. 4, 2009 issue of the journal Nature Medicine, could not only prove a very useful method to faithfully reproduce different types of tumors but also to elucidate the nature of elusive cancer stem cells. The most frequently used mouse cancer model relies on xenografts: Human tumor tissue or cancer cell lines are transplanted in immuno-compromised mice, which quickly develop tumors. "These tumors are very reproducible, but this approach ignores the fact that the immune system can make or break cancer," says first author Tomotoshi Marumoto, Ph.D., a former postdoctoral researcher in the Verma lab and now an assistant professor at the Kobe Medical Center Hospital in Kobe, Japan. Other animal models either express oncogenes in a tissue-specific manner or shut down the expression of tumor suppressor genes in the whole tissue. "But we know that tumors generally develop from a single cell or a small number of cells of a specific cell type, which is one of the major determinants of the characteristics of tumor cells," explains postdoctoral researcher and co-author Dinorah Friedmann-Morvinski. To sidestep the shortcomings of currently used cancer models, the Salk team harnessed the power of lentiviral vectors to infect nondividing as well as dividing cells and ferry activated oncogenes into a small number of cells in adult, fully immunocompetent mice. After initial experiments confirmed that the approach was working, Marumoto injected lentiviruses carrying two well-known oncogenes, H-Ras and Akt, into three separate brain regions of mice lacking one copy of the gene encoding the tumor suppressor p53: the hippocampus, which is involved in learning and memory; the subventricular zone, which lines the brain's fluid-filled cavity; and the cortex, which governs abstract reasoning and symbolic thought in humans. He specifically targeted astrocytes, star-shaped brain cells that are part of the brain's support system. They hold neurons in place, nourish them, digest cellular debris, and are suspected to be the origin of glioblastoma. Within a few months, massive tumors that displayed all the histological characteristics of glioblastoma multiforme preferentially developed in the hippocampus and the subventricular zone. The ability of adult stem cells to divide and generate both new stem cells ( called self-renewal ) as well as specialized cell types ( called differentiation ) is the key to maintaining healthy tissues. The cancer-stem-cell hypothesis posits that cancers grow from stem cells in the same way healthy tissues do. Known as tumor-initiating cells with stem like properties these cells have many characteristics in common with normal stem cells in that they are self-replicating and capable of giving rise to populations of differentiated cells. To test whether the induced glioblastomas contained bona fide cancer stem cells, Marumoto isolated cultured individual tumor cells in the lab. These cells behaved and looked just like neural stem cells. They formed tiny spheres—often called tumor spheres—and expressed proteins typically found in immature neural progenitor cells. When given the right chemical cues, these brain cancer stem cells matured into neurons and astrocytes. "They displayed all the characteristics of cancer stem cells, and less than 100 and as few as 10 cells were enough to initiate a tumor when injected into immunodeficient mice," says Friedmann-Morvinski. Most xenograft models for brain tumors using tumor cell lines require at least 10,000 cells. "These findings show that our cancer model will not only allow us to start understanding the biology of glioblastoma but will also allow us to answer many questions surrounding cancer stem cells," says Verma. Although the work described to date pertains to glioblastoma, Verma and his team are currently using this methodology to investigate lung, pancreatic, and pituitary cancers. Authors who also contributed to the work include Ayumu Tashiro, Ph.D., at the Kavli Institute for Systems Neuroscience at the Medical Technical Research Center in Trondheim, Norway; Miriam Scadeng, Ph.D., at the UCSD Center for Functional MRI in La Jolla; Yasushi Soda, Ph.D.; and Fred H. Gage in the Laboratory of Genetics at the Salk Institute. This work was supported by the National Institutes of Health and in part by the H. N. and Frances C. Berger Foundation. The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health, and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes. For information on the commercialization of this technology, please contact Dave Odelson at 858-453-4100, x 1223 ( dodelson@salk.edu ) in of the Salk Office of Technology Management and Development.

Why our body resists cancer-killing viruses

Friday, 13 June , 2008, 12:32

Washington: Viruses designed to treat incurable brain tumours like glioblastoma were stumped by how the immune system eliminated them at the outset. Now an animal study conducted by Ohio State University researchers helps explain why this happened, a development that could help improve therapy for brain cancer patients. The study shows how viruses that destroy the tumour cells also cause them to throw up proteins stimulating growth of new tumour blood vessels. These vessels transport immune cells that eradicate the viruses, stimulating tumour re-growth. “This study points to an important side-effect of oncolytic viral therapy that may limit its efficacy,” said Balveen Kaur, who was part of the research team. “We can now work on designing a combination therapy that will inhibit this effect and enhance the action of the viral therapy.” The findings of the study have been published in the latest issue of the journal Molecular Therapy.

Recurrent Brain Cancer Responds To New Treatment

ScienceDaily (2008-02-29) -- One of the toughest cancers to treat effectively is glioblastoma multiforme (GBM), the most common form of primary brain cancer. Patients who have a recurrence of this cancer have had no effective therapy -- until now. Researchers have discovered that a compound has shown the ability to effectively treat GBM in some patients.

Gene Therapy “Trains” Immune System to Destroy Brain Cancer Cells and Reverses Behavioral Deficits

Description
A new gene therapy approach that attracts and “trains” immune system cells to destroy deadly brain cancer cells also provides long-term immunity, produces no significant adverse effects and -- in the process of destroying the tumor -- promotes the return of normal brain function and behavioral skills, according to a study conducted by researchers at Cedars-Sinai Medical Center’s Board of Governors Gene Therapeutics Research Institute.