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GENES & HUMANS: Cancer-fighting GE virus shown to target tumors alone



                                  PART 1


------------------------------- GENET-news -------------------------------

TITLE:   CANCER-FIGHTING VIRUS SHOWN TO TARGET TUMORS ALONE

SOURCE:  Thomson Reuters, USA

AUTHOR:  Deena Beasley

URL:     http://www.reuters.com/article/2011/08/31/cancer-virus-idUSN1E77T14Z20110831

DATE:    31.08.2011

SUMMARY: "Researchers have shown for the first time that a single intravenous infusion of a genetically engineered virus can home in on cancer, killing tumor cells in patients without harming healthy tissue. Scientists have been intrigued for decades with the idea of using viruses to alert the immune system to seek and destroy cancerous cells. That interest has taken off in recent years as advances in genetic engineering allow them to customize viruses that target tumors. The field received a boost in January when biotech giant Amgen Inc agreed to pay up to $1 billion for BioVex, the developer of experimental cancer-fighting virus OncoVex. But the only ?oncolytic virus? so far approved by a regulatory agency is for treatment of head and neck cancer in China."

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CANCER-FIGHTING VIRUS SHOWN TO TARGET TUMORS ALONE

- Small trial shows virus hits cancer, spares normal cells

- Mid-stage trial in liver cancer patients under way

- Another big step in ?customizing? viruses to target tumors

Aug 31 (Reuters) - Researchers have shown for the first time that a single intravenous infusion of a genetically engineered virus can home in on cancer, killing tumor cells in patients without harming healthy tissue.

Scientists have been intrigued for decades with the idea of using viruses to alert the immune system to seek and destroy cancerous cells. That interest has taken off in recent years as advances in genetic engineering allow them to customize viruses that target tumors.

The field received a boost in January when biotech giant Amgen Inc agreed to pay up to $1 billion for BioVex, the developer of experimental cancer-fighting virus OncoVex. But the only ?oncolytic virus? so far approved by a regulatory agency is for treatment of head and neck cancer in China.

In a study published in the journal Nature on Wednesday, scientists at institutions including the University of Ottawa and privately held biotech company Jennerex Inc said a small, early-stage trial of experimental viral therapy JX-954 found that it consistently infected tumors with only minimal and temporary side effects.

The experimental virus will next be tested in a mid-stage trial of patients with liver cancer.

?With chemotherapy you get drastic side effects,? said Dr. John Bell, chief scientific officer at Jennerex and senior scientist at the Ottawa Hospital Research Institute. ?Patients on this treatment only had 24-hour flu symptoms, and nothing after that.?

The trial, which involved 23 patients with various types of advanced cancer, was designed to assess the safety of JX-954. It also found that six of the eight patients given the two highest doses saw their tumors stabilize or shrink.

Seven patients in that group, or 87 percent, had evidence of viral replication in their tumors, but not in normal tissues.

Dr. Bell said the next step is a Phase 2b trial of the viral therapy in 120 patients with primary liver cancer, known as hepatocellular carcinoma.

He said earlier trials of JX-954 showed really strong activity in liver cancer. Since some kinds of liver cancer are caused by viruses -- like hepatitis B -- the theory is that those tumor cells may be more susceptible to a second virus.

JX-954 is derived from a strain of the virus once commonly used to vaccinate children against smallpox.

?We know it is pretty safe,? Dr. Bell said, noting that genetic information needed for the virus to mutate has been deleted from JX-954.

He also said that because the Jennerex virus can be given intravenously, spreading throughout the body, it may hold promise for limiting the ability of cancer cells to metastasize and spread.

Other viral cancer therapies are also progressing in clinical trials, but they either require direct injection into the tumor or accompany chemotherapy. Results from a Phase 3 melanoma trial of Amgen?s OncoVex, which is directly injected into tumors, are expected next year.

Oncolytics Biotech Inc is conducting a pivotal trial of its experimental virus, Reolysin, in combination with chemotherapy for patients with head and neck cancer.

?We are all competing against standard of care,? said Matt Coffey, chief operating officer at Oncolytics Biotech.

Jennerex is primarily funded by investors from Canada and South Korea. European rights to JX-954 have been licensed to Transgene. Other regional licenses are held by Lee?s Pharmaceutical Ltd for China and Green Cross Corp for South Korea. Jennerex has not licensed rights in the United States or Japan. (Editing by Michele Gershberg, editing by Matthew Lewis)



                                  PART 2

------------------------------- GENET-news -------------------------------

TITLE:   MODIFIED SMALLPOX VACCINE TARGETS CANCER CELLS WHILE MISSING HEALTHY ONES

SOURCE:  Bloomberg, USA

AUTHOR:  Ryan Flinn

URL:     http://www.bloomberg.com/news/2011-08-31/modified-smallpox-virus-can-target-cancer-cells-while-missing-healthy-ones.html

DATE:    31.08.2011

SUMMARY: "A genetically modified smallpox vaccine was able to target and shrink tumors in some cancer patients while leaving healthy cells unharmed, in the first study to show the potential of using a virus to fight human malignancies. Almost two-dozen patients with advanced cancers were injected with varying amounts of the virus, called JX-594, and six participants in the highest dose group had their tumors stabilize or shrink, according to the report released today by the journal Nature."

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MODIFIED SMALLPOX VACCINE TARGETS CANCER CELLS WHILE MISSING HEALTHY ONES

A genetically modified smallpox vaccine was able to target and shrink tumors in some cancer patients while leaving healthy cells unharmed, in the first study to show the potential of using a virus to fight human malignancies.

Almost two-dozen patients with advanced cancers were injected with varying amounts of the virus, called JX-594, and six participants in the highest dose group had their tumors stabilize or shrink, according to the report released today by the journal Nature.

The trial demonstrated that a virus injected into the blood stream could infect and spread within tumors without harming other cells, said John Bell, one of the study?s authors and a cancer research scientist at Ottawa Hospital Research Institute. Results were from the first of three testing stages generally required for regulatory approval.

?It?s never been shown before that we could do this in humans,? Bell said in an interview. ?We even see in some patients a modest therapeutic benefit.?

Researchers used the same strain of virus that?s used in the smallpox vaccine, called vaccinia virus, because of its natural ability to replicate itself in cancer cells, the report said. They then modified it to enhance its cancer-fighting properties.

While vaccinia virus is similar to smallpox, it doesn?t contain smallpox and can?t cause the disease, according to the U.S. Centers for Disease Control and Prevention.

New Approach

The approach differs from so-called cancer vaccines, such as Merck & Co.?s Gardasil shot that targets a virus that causes cervical cancer or Dendreon Corp.?s Provenge, which stimulates an immune response against prostate cancer cells.

The therapy, developed by closely held San Francisco-based Jennerex Inc., will be tested in a broader trial, said Bell, who co-founded Jennerex and is its chief scientific officer. If successful, the method could help patients whose cancer has spread beyond one area.

?The big problem with cancer is not people showing up with one tumor you can excise with a scalpel, the problem is metastatic disease that you can?t even see where it is,? he said. ?By putting the virus in the blood system, it allows the virus to go around and potentially find all the fertile ground for it to grow in, all the places tumors are, and once it does that, it can affect them all and destroy them.?

Some patients in the trial had side effects such as mild to moderate flu-like symptoms that lasted less than one day, according to the report. Jennerex, the Terry Fox Foundation, the Canadian Institutes of Health Research and the Ontario Institute for Cancer Research and others financed the study.

Jennerex has enough cash to run the next set of experiments, and will likely look for additional funds later, Bell said. The company?s name is based on Edward Jenner, an 18th century English scientist who developed the first vaccination with an inoculation against the related cow-pox virus.



                                  PART 3

------------------------------- GENET-news -------------------------------

TITLE:   OTTAWA RESEARCHER?S TUMOUR-ATTACKING VIRUS SHOWS PROMISE AS CANCER TREATMENT

SOURCE:  Ottawa Citizen, Canada

AUTHOR:  Pauline Tam

URL:     http://www.ottawacitizen.com/health/Ottawa+researcher+tumour+attacking+virus+shows+promise+cancer+treatment/5334274/story.html

DATE:    31.08.2011

SUMMARY: "An experimental, made-in-Ottawa virus that attacks tumours has been shown to be a safe and potentially useful drug against hard-to-treat cancers, justifying further trials in more patients. Early results even raise the possibility that the treatment could actually prevent the spread of tumours ? a long-desired goal in the hunt for better cancer therapies. John Bell, a senior scientist at The Ottawa Hospital Research Institute and University of Ottawa, is working on a cancer-killing virus genetically engineered from a version used to vaccinate against smallpox."

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OTTAWA RESEARCHER?S TUMOUR-ATTACKING VIRUS SHOWS PROMISE AS CANCER TREATMENT

OTTAWA ? An experimental, made-in-Ottawa virus that attacks tumours has been shown to be a safe and potentially useful drug against hard-to-treat cancers, justifying further trials in more patients.

Early results even raise the possibility that the treatment could actually prevent the spread of tumours ? a long-desired goal in the hunt for better cancer therapies.

John Bell, a senior scientist at The Ottawa Hospital Research Institute and University of Ottawa, is working on a cancer-killing virus genetically engineered from a version used to vaccinate against smallpox.

In the first phase of a lengthy process to test the drug?s safety and effectiveness, the virus-based drug, called JX594, appeared to cause no lasting harm to cancer patients whose tumours were resistant to conventional chemotherapy and radiation.

The only observed side effects were flu-like symptoms, such as fever, chills, fatigue, headache, nausea and vomiting, which lasted up to 24 hours and could be treated with over-the-counter drugs such as acetaminophen. ?There were no long-term side effects that we could see at all,? said Bell.

More significantly, the virus showed signs of quickly infecting and killing cancer cells, while protecting healthy cells, which current therapies can?t do.

The virus also appeared as capable of attacking isolated tumours as those spread throughout the body, which are the toughest to treat.

Bell?s team proved this by injecting the virus into the bloodstreams of 23 terminal cancer patients, all with metastatic tumours that had resisted standard forms of treatment. The only cancer the virus couldn?t fight was leukemia.

Within two weeks of receiving a single dose of the drug, biopsies showed the tumour-fighting virus was multiplying in seven of the patients who were given the highest dosages. And scans later showed that tumours in six of the patients were shrinking or had stopped growing.

The results of the Phase 1 trial, in which a drug?s safety for patients is assessed, were published Wednesday in Nature, a top science journal. Because only a handful of patients were studied in the trial, Bell and his research team must do further tests on hundreds more patients to show the treatment actually works.

Some biologists have expressed skepticism about cancer-targeting viruses, saying the body?s immune system would kill the virus before it could kill the tumours.

Indeed, Bell acknowledged the possibility that patients who are given repeated doses of the virus could develop such potent immunity to it that the treatment no longer works. For that reason, he is in the early stages of testing second-line viruses that could replace JX594.

However, Bell?s research team has also shown that the virus-based drug can stimulate the body?s immune system to recognize and attack tumours and, perhaps, even prevent them from redeveloping once killed. That raises the possibility that the treatment could actually stop the spread of tumours.

?In mouse models, we?ve shown that if we treat with this virus and cure the tumour in mice, the mice develop immunity to the tumour,? said Bell. ?The question is, will we see that in people? We don?t know the answer to that yet.?

Cancer-killing viruses have a long and checkered history in cancer therapy ? perceived as safe but ineffective. To date, no cancer-targeting virus has been approved as a treatment for the disease.

Yet interest in such viruses was revived earlier this year, when the U.S. biotechnology giant Amgen paid $425 million to acquire BioVex, a Massachusetts-based company that is in the final phase of testing a tumour-busting virus.

Approval of Amgen?s virus by U.S. drug regulators would significantly improve the prospects for Bell?s own virus.

Bell has established a San Francisco-based spin-off company, Jennerex Inc., to commercialize his experimental therapy.

A Phase 2 trial is to start this month for up to 140 patients in Canada, the U.S., Korea and Europe. It is aimed at patients with end-stage liver or colon cancer, who will be randomly assigned to receive either the experimental treatment, or standard forms of therapy.

In order for the virus to be approved for commercial use, the trial must determine if the virus can prolong a patient?s life for longer than existing therapies can. The current prognosis for most liver-cancer patients is six months. ?We?re hoping to do better than that with our therapy,? said Bell.



                                  PART 4

------------------------------- GENET-news -------------------------------

TITLE:   RESULTS OF WORLD-FIRST VIRAL THERAPY TRIAL IN OTTAWA CANCER PATIENTS PUBLISHED IN NATURE

SOURCE:  Ottawa Hospital Research Institute, Canada

AUTHOR:  Press Release

URL:     http://www.ohri.ca/newsroom/newsstory.asp?ID=269

DATE:    31.08.2011

SUMMARY: "Researchers from the Ottawa Hospital Research Institute (OHRI), the University of Ottawa (uOttawa), Jennerex Inc. and several other institutions today reported promising results of a world-first cancer therapy trial in renowned journal Nature. The trial is the first to show that an intravenously-delivered viral therapy can consistently infect and spread within tumours without harming normal tissues in humans. It is also the first to show tumour-selective expression of a foreign gene after intravenous delivery."

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RESULTS OF WORLD-FIRST VIRAL THERAPY TRIAL IN OTTAWA CANCER PATIENTS PUBLISHED IN NATURE

Researchers from the Ottawa Hospital Research Institute (OHRI), the University of Ottawa (uOttawa), Jennerex Inc. and several other institutions today reported promising results of a world-first cancer therapy trial in renowned journal Nature. The trial is the first to show that an intravenously-delivered viral therapy can consistently infect and spread within tumours without harming normal tissues in humans. It is also the first to show tumour-selective expression of a foreign gene after intravenous delivery.

The trial involved 23 patients (including seven at The Ottawa Hospital), all with advanced cancers that had spread to multiple organs and failed to respond to standard treatments. The patients received a single intravenous infusion of a virus called JX-594, at one of five dose levels, and biopsies were obtained eight to 10 days later. Seven of eight patients (87 per cent) in the two highest dose groups had evidence of viral replication in their tumour, but not in normal tissues. All of these patients also showed tumour-selective expression of a foreign gene that was engineered into the virus to help with detection. The virus was well tolerated at all dose levels, with the most common side effect being mild to moderate flu-like symptoms that lasted less than one day.

?We are very excited because this is the first time in medical history that a viral therapy has been shown to consistently and selectively replicate in cancer tissue after intravenous infusion in humans,? said Dr. John Bell, a Senior Scientist at OHRI, Professor of Medicine at uOttawa and senior co-author on the publication. ?Intravenous delivery is crucial for cancer treatment because it allows us to target tumours throughout the body as opposed to just those that we can directly inject. The study is also important because it shows that we can use this approach to selectively express foreign genes in tumours, opening the door to a whole new suite of targeted cancer therapies.?

Dr. Bell and his team have been investigating cancer-fighting (oncolytic) viruses at OHRI for more than 10 years. JX-594 was developed in partnership with Jennerex Inc., a biotherpeutics company co-founded by Dr. Bell in Ottawa and Dr. David Kirn in San Francisco. JX-594 is derived from a strain of vaccinia virus that has been used extensively as a live vaccine against smallpox. It has a natural ability to replicate preferentially in cancer cells, but it has also been genetically engineered to enhance its anti-cancer properties.

?Oncolytic viruses are unique because they can attack tumours in multiple ways, they have very mild side effects compared to other treatments, and they can be easily customized for different kinds of cancer,? said Dr. Bell. ?We?re still in the early stages of testing these viruses in patients, but I believe that someday, viruses and other biological therapies could truly transform our approach for treating cancer.?

Although the current trial was designed primarily to assess safety and delivery of JX-594, anti-tumour activity was also evaluated. Six of eight patients (75 per cent) in the two highest dose groups experienced a shrinking or stabilization of their tumour, while those in lower dose groups were less likely to experience this effect.

?These results are promising, especially for such an early-stage trial, with only one dose of therapy,? said Dr. Bell. ?But of course, we will need to do more trials to know if this virus can truly make a difference for patients. We are working hard to get these trials started, and at the same time, we are also working in the laboratory to advance our understanding of these viruses and figure out how best to use them.?

?On behalf of everyone involved in this research, I want to thank all the courageous patients who participated in this trial,? added Dr. Bell. I also want to thank the community and funding organizations for their generous support.?

About the Study Funders and Authors

This research was supported by Jennerex Inc., the Terry Fox Foundation, the Canadian Institutes of Health Research, the Ontario Institute for Cancer Research, The Ottawa Hospital Foundation, the Canada Foundation for Innovation, the Natural Sciences and Engineering Research Council of Canada and the Republic of Korea. OHRI / uOttawa authors on the paper include Dr. John Bell, Dr. Derek Jonker, Dr. Laura Chow, Dr. Fabrice Le Boeuf, Joe Burns, Laura Evgin, Naomi De Silva, Sara Cvancic, Dr. Kelley Parato, Dr. Jean-Simon Diallo and Dr. Manijeh Daneshmand, as well as alumnus Dr. Caroline Breitbach. Other authors are listed in the full publication, available at www.nature.com.

About OHRI

The Ottawa Hospital Research Institute (OHRI) is the research arm of The Ottawa Hospital and is an affiliated institute of the University of Ottawa, closely associated with the University?s Faculties of Medicine and Health Sciences. The OHRI includes more than 1,500 scientists, clinical investigators, graduate students, postdoctoral fellows and staff conducting research to improve the understanding, prevention, diagnosis and treatment of human disease. www.ohri.ca

Note: Patients interested in participating in clinical trials should discuss this with their oncologist. Dr. Bell is not a medical doctor and is not able to enroll patients in clinical trials.