Source: Federation Of European Cancer Societies
Date: 2003-09-23
http://www.sciencedaily.com/releases/2003/...30923065908.htm


First Steps Towards A Vaccine For Pancreatic Cancer.

Link: http://www.epeiusbiotech.com/news_090303.html

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LOS ANGELES, Calif. and Manila, Philippines, August 23, 2003
EPEIUS BIOTECHNOLOGIES CORPORATION GAINS FDA ORPHAN DRUG APPROVAL FOR REXIN-GTM, THE WORLD'S FIRST TARGETED INJECTABLE GENE THERAPY VECTOR, FOR PANCREATIC CANCER.

LOS ANGELES, California, August 22, 2003 - Epeius Biotechnologies Corporation ("Epeius" www.epeiusbiotech.com) today announced that the FDA has approved REXIN-GTM , the world's first tumor-targeted injectable gene therapy vector, as an orphan drug for pancreatic cancer. The FDA's decision to approve REXIN-GTM was based on objective demonstrations of medical plausibility of REXIN-GTM as an effective treatment for pancreatic cancer. The major benefit to the company is market exclusivity for the REXIN-GTM product for all types of pancreatic cancer. This represents a highly significant milestone for Epeius Biotechnologies since its lead product, REXIN-GTM, is the first gene therapy product to gain FDA orphan drug designation for pancreatic cancer.

Epeius also announced that the Company has executed a screening agreement with the National Cancer Institute wherein NCI scientists will evaluate the activity of REXIN-GTM and other promising targeted gene therapy products at the NCI. In an interview with Dr. Frederick L. Hall, President and CEO of Epeius Biotechnologies, Dr. Hall emphasized that "Federal and State support is vital to an emerging biotech company like Epeius, to expedite the advancement of REXIN-GTM and other targeted genetic medicines to the clinic for the benefit of cancer patients. The screening agreement is an important first step.

ABOUT EPEIUS: The mission of Epeius Biotechnologies is to develop and commercialize the first truly effective Targeted Delivery System (TDS) that can be injected directly into a vein to deliver genes and molecular therapeutics preferentially to cancerous tumors that have spread throughout the body (metastatic cancer), without eliciting systemic side effects or organ damage. REXIN-GTM is the first targeted injectable gene therapy vector that has been approved by both the U.S. FDA and the Philippine BFAD (FDA counterpart) for use in Phase I/II cancer clinical trials. The encouraging results of the first human experience using REXIN-GTM as intravenous infusions for advanced pancreatic cancer will be presented at the SRI Nucleic Acid World Summit meeting in Boston on September 16, 2003 by Dr. Erlinda M. Gordon, Medical Director of Epeius.

Link: http://www.eurekalert.org/pub_releases/200...s-dra051204.php

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Public release date: 15-May-2004
Contact: Andy Nordhoff
DMS.Communications@Dartmouth.edu
603-653-1969
Dartmouth Medical School

Dartmouth researchers advance fight against pancreatic cancer
New studies show success in reducing tumor growth

LEBANON, NH -- Two Dartmouth medical studies have produced promising results in the fight against pancreatic cancer, one of the most deadly and aggressive forms of cancer, and may lead to the development of new, highly targeted therapies to manage previously untreatable tumors.

In two trials targeting some of the most challenging traits of pancreatic tumor cell growth, researchers from Dartmouth Medical School (DMS) and the Norris Cotton Cancer Center (NCCC) at Dartmouth-Hitchcock Medical Center (DHMC) have demonstrated success in slowing and preventing tumor development.

The NCCC research team was led by Dr. Murray Korc, a pioneer in early research on growth factor receptors in pancreatic cancer, and chair of the department of medicine at DMS and DHMC. An endocrinologist and cancer biologist, he focuses much of his research on the mechanisms that make pancreatic cancer so resilient and aggressive. Work reported in the May 15 issues of Clinical Cancer Research and Cancer Research addresses the team's latest advances.

Pancreatic cancer is characteristic for its ability to spread quickly, while becoming increasingly resistant to traditional chemotherapy. Generally diagnosed in an advanced state, it is frequently inoperable. As a result, it is the fourth leading cause of cancer death in adults in the US, killing more than 30,000 Americans every year, says Korc.

"By the time the disease is diagnosed, pancreatic cancer cells have a huge growth advantage over normal cells, which enables them to grow and metastasize very quickly," said Korc. "Our research has focused on determining what factors enable the cells to grow at such a fast rate and then how to slow that rate down and actually suppress pancreatic tumor growth."

Korc likens the disease to speeding in a car with an accelerator that is stuck to the floor. "Naturally, you apply the brakes but they don't work, so you begin pumping the brakes to slow the car down. The brakes are broken in pancreatic cancer but in addition, we found that the brake has been converted into an accelerator by the cancer cells. In essence, pumping the brakes gives you two accelerators."

In fact, said Korc, the inhibitory factors that have been proven to slow down the growth of normal cells, can often backfire and increase the spread of tumors in the pancreas, or in other words, change the brake into an accelerator.

In a feature article appearing in the May 15 edition of Clinical Cancer Research, Korc and Dr. Mitsuharu Fukasawa, a research associate in the department of medicine at DMS, reported a new, highly effective anti-angiogenic approach for treating pancreatic cancer. They focused on the over-expression of a molecule that hampers chemotherapeutic efforts in pancreatic cancer. The molecule, VEGF, is responsible for angiogenesis, a process that stimulates blood vessel formation. In pancreatic cancer cells, there is a 90-fold higher level of VEGF than in normal cells, which enables the cancer cells to grow and metastasize quickly and efficiently.

In this study, the researchers injected a protein sponge, VEGF-Trap, into mice bearing pancreatic tumors derived from four different human pancreatic cancer cells. They predicted the sponge would absorb most of the angiogenetic VEGF molecules, thereby slowing the blood vessel proliferation and suppressing tumor growth.

"The protein sponge completely suppressed pancreatic tumor growth," said Korc. "In all the tumors tested, there was a marked decrease in blood vessel formation, which is very exciting." The next step, he acknowledged, is to introduce this technology in humans, where it is desperately needed.

In the second study, published in Cancer Research, Korc and his research team, headed by his post-doctoral fellow Nicole Boyer Arnold, describe a novel mechanism for chemoresistance in pancreatic cancer. In their investigation, the team identified the pathways responsible for giving the pancreatic cancer cells a growth advantage and making them resistant to chemotherapeutic drugs. They focused on two molecules, Smad7 and thioredoxin, which are found in high quantities in many pancreatic tumors.

These molecules make signaling pathways abnormal so that when a drug is introduced to suppress cancer cell growth, these molecules allow the cancer cells to resist the drugs and to continue to grow. This chemo-resistance is a hallmark of aggressive cancers such as pancreatic cancer. "Now that we know this pathway exists, it will allow us and other investigators to try to figure out ways to interfere with this pathway to design new therapies for pancreatic cancer," said Korc. In future research, the research team will also introduce a molecular sponge to absorb certain over-expressed molecules that promote the expression of Smad7 and thioredoxin, in order to determine if this renders the cancer cells more responsive to therapy.

Although these studies are early, Korc is hopeful they will develop into clinical trials in the future. "The mortality rate (of pancreatic cancer) virtually equals incidence," he said. "Of the 31,000 people in the US that get it this year, 30,300 will die from it, and most patients die within six months. That is why we are excited about this research and hope that it will lead to more advances in the treatment of pancreatic cancer."


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The studies were funded by the National Cancer Institute through two United States Public Health Service Grants awarded to Korc, and by a postdoctoral fellowship to DMS/NCCC researcher Nicole Boyer Arnold from the George E. Hewitt Foundation for Medical Research.

http://www.eurekalert.org/bysubject/biology.php

Pancreatic cancer blood test & gene studies show promise

Link: http://www.newscientist.com/news/news.jsp?...p?id=ns99995067

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Gene therapy to treat deadly cancer
17:39 02 June 04
NewScientist.com news service

The world's first gene therapy trial to treat patients with pancreatic cancer is being launched in the UK. The therapy uses a "Trojan horse" technique to hit cancer cells with large doses of toxic drugs.

MetXia, developed by UK company Oxford BioMedica, consists of a retrovirus which has been modified to carry a gene for an enzyme that normally occurs in the liver.

Retroviruses only replicate in dividing cells, so the treatment mainly targets cancer cells. Once in the cell, the virus inserts the gene for the enzyme and the cell starts producing it. The enzyme then converts an inactive drug into a toxic form.

This obliterates the tumour cells, without harming normal ones. It also means a hugely increased dose of chemotherapy can be delivered to tumours, without patients suffering greater harmful effects.

"In the industrialised world there are at least a quarter of a million people a year dying from pancreatic cancer," says John Neoptolemos, professor of surgery at the University of Liverpool, UK, who is leading the trial. "The horrible thing about pancreatic cancer is that if you have advanced disease, and you usually do, you can predict the date of death within a matter of a few weeks."

Alan Kingsman, chief executive of Oxford BioMedica, says: "We are really excited about the pancreatic cancer trial. We have reason to believe that MetXia may be quite potent in that type of cancer."


Source of destruction

Work in animal models of pancreatic cancer and in the test tube have shown promising results for MetXia. And early clinical trials to test its safety in patients with breast cancer and melanoma have also been encouraging.

The modified retrovirus carries a gene for an enzyme known as cytochrome P450 which is essentially a detoxifying gene, says Neoptolemos. The enzyme converts an inactive chemotherapy drug called cyclophosphamide into toxic phosphoramide mustard and acrolein.

Neoptolemos and his team are currently recruiting nine patients for a "proof of principle" trial - to test that the virus is indeed taken up by cancer cells when injected either locally or systemically.

After a day or two, the patients will then be given cyclophosphamide, which should be converted into the toxic form in the cancer cells only. If the first trial is successful, the team will then run a safety trial in 20 to 40 patients.

Bubble boys

Progress in gene therapy has been faltering in the past few years. Safety concerns over inserting new genes were raised when some boys being treated for X-SCID - "bubble boy" syndrome - unexpectedly developed leukaemias during a French trial in 2003.

And on 28 May, a hemophilia gene therapy trial by Avigen was halted because of safety issues.

But Neoptolemos says that MetXia is a different type of gene therapy. "This is a different type of gene therapy in the sense that we are not replacing a lost gene."

"We are actually killing the cell," he says. "Normally you can't get enough of the drug into the cell because of the drug-resistant mechanisms of cancer cells - but here we are able to deal with that."


Shaoni Bhattacharya

http://www.eurekalert.org/bysubject/medicine.php

Researchers identify two potential protein targets for new drug therapies for pancreatic cancer

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