Archive for the ‘vaccine’ Category

Penn researchers enlist dogs in battle against human cancers

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Posted 14 Jul 2012 — by James Street
Category Dog Osteosarcoma, listeria bacteria, vaccine
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Posted: Sat, Jul. 14, 2012, 3:01 AM

By Faye Flam

Inquirer Staff Writer

Penn veterinarian Nicola Mason, left, with Sasha and the dog

TOM GRALISH / Staff Photographer
Penn veterinarian Nicola Mason, left, with Sasha and the dog’s owners, Carlos and Liliana Ruano. Sasha lost a foreleg to bone cancer and is now receiving experimental treatment.
HEALTH
 

 Sasha is still spunky at 12 – a white dog with a smattering of black, floppy ears and a sweet face. Even after she lost her right foreleg to bone cancer, her owners said, she could jump and catch a Frisbee. Unfortunately, in nearly all cases like Sasha’s, the surgery offers just a short respite before the cancer comes roaring back. Her only hope now lies with an experimental treatment being developed at the University of Pennsylvania.

Tuesday, doctors at Penn’s School of Veterinary Medicine pumped a modified listeria bacteria into her bloodstream, hoping to push her immune system to kill remaining cancer cells. If the treatment works, it is likely to be tested next on humans with this type of bone cancer, called osteosarcoma.

Veterinary scientists say such cross-species research is on the rise. While animal research has long played an important role in human medicine, an increasing number of clinical trials for dogs are being designed to help both species.

Right now, the vast majority of cancer treatments that work in mice fail in people, said immunologist Carl June, director of translational research at Penn’s Abramson Cancer Center. By testing the treatments in dogs, he said, veterinarians are helping sort out the potential winners.

Osteosarcoma is also easier to study in dogs because it’s relatively common, especially in larger breeds. In humans, it’s an orphan disease, but it takes a vicious toll. It strikes young people, most of them between the ages of 13 and 25. Often their only hope for survival is a radical amputation.

Liliana Ruano said she and her husband, Carlos, wanted a dog that could accompany the North Carolina couple on hiking and camping adventures, and Sasha turned out to be just perfect. They often visit Carlos’ family in Pennsylvania and hike with Sasha in French Creek State Park.

The first sign of trouble came earlier this year, when Sasha started limping. The local veterinarian thought it was an injury; it seemed to get better for awhile, but then it got much worse.

An X-ray revealed bone cancer, and the doctor offered grim choices. They could do nothing and their faithful hiking buddy would die in agony, or they could amputate the leg, which would give her a few months of pain-free life before the cancer returned, usually as a fatal chest tumor. Mild chemotherapy would extend her life slightly.

They opted for the surgery and chemotherapy, and Sasha came through very well. She’s running around and playing Frisbee – for now, anyway.

Concerned that Sasha’s cancer would come back, Liliana found information about the Penn trial on a Facebook page about dogs and cancer. She called to find out more and connected with Nicola Mason, who explained the treatment, its risks and benefits. Mason told them the tumor would have to be of a certain type for Sasha to qualify – expressing a marker called her2/neu. Sasha’s tumor tested positive.

Mason, who has both a veterinary degree and a doctorate in immunology, said osteosarcoma tumors that strike dogs are very similar to those that strike humans. Dog and human lymphomas are also similar, and she is also involved in a trial to treat dog lymphoma.

Treatment with listeria bacteria might sound scary because it’s associated with food poisoning, but it is disabled, Mason said. “It’s modified so it does not cause disease and is rapidly cleared.” But it should still prompt an immune response in Sasha.

Modified listeria has been tested in mice and used in some trials connected with human cervical cancer, she said. For this treatment, the listeria was also genetically modified – a gene was added to allow the bacteria to make a protein called her2/neu – the same one they tested for and was expressed in Sasha’s tumor.

The idea is to train the patient’s immune system with the her2/neu protein the way you might train a bloodhound with a piece of someone’s clothing. The immune cells are geared to attack listeria, but they will also be trained to recognize and attack cancer cells that express the her2/neu. This protein is one of the few marks that distinguishes the cancer cells from healthy ones, so the immune system should go after the cancer.

Though Sasha looks healthy now, amputations almost always leave behind a few malignant cells, which is why dogs often bounce back after an amputation but almost always get a fatal recurrence.

“They are sitting on time bombs,” Mason said. In virtually all cases, stray malignant cells eventually spread to the lungs and kill the dog. “What we’re doing with the immunotherapy is mopping up the cancer cells we can’t see,” she said. So far, they’ve signed up six dogs, and they aim to recruit 9 to 18.

Why can’t the immune system kill the cancer cells without all this help?

Our immune systems do best when fighting foreign cells, said the University of Minnesota’s Jaime Modiano, who is, like Mason, a veterinarian with a doctorate in immunology. Cancer cells are so similar to our own cells that it can be hard for the immune system to recognize them as invaders.

In a given patient, canine or human, cancer cells undergo their own version of natural selection. The ones that evade the immune system survive and proliferate, he said. Cancer cells can evolve a host of evasive maneuvers. The challenge with immunotherapy is getting around all those tricks.

Modiano says clinical trials elsewhere are testing new therapies for brain cancer and other malignancies that strike both canines and humans. Working with dogs gives them information they couldn’t get studying mice or people, he said. There is no shortage of dogs with spontaneous cases, he said, since cancer strikes about one in three dogs.

Studying dogs also allows researchers to learn at an accelerated pace – literally in dog years. If a treatment keeps a terminally ill dog alive for two years, that’s like keeping a human alive for 10 or 15 years.

Penn’s Carl June sees clinical trials with dogs as a way to take advantage of an explosion of untested but promising new approaches to fighting cancer and to accelerate the process of sorting the winners from the losers.

Immune therapies are a good case in point, he said. “This is exactly the sort of thing that should be done on a dog,” he said.

No other large animals routinely get cancer the way dogs and humans do. Monkeys rarely get cancer spontaneously, and many people have ethical concerns about giving cancer to fellow primates. Scientists see some striking similarities in the genetics and biology of dog and human cancers. Cats, too, are starting to be entered in clinical trials, but Mason said dog research is further ahead.

Sasha had her first treatment at Penn on Tuesday. She will stay several days for observation before her owners take her back to North Carolina.

Liliana Ruano says she understands the risks and potential benefits. “Dr. Mason spent a lot of time with us to make sure we were comfortable,” she said. Ultimately, she decided to go ahead because of the chance to extend Sasha’s life. “I’m not ready to let her go yet.”

 

Dogs With Cancer Helping to Find a Cure

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Posted 03 Dec 2011 — by James Street
Category Dog Osteosarcoma, Osteosarcoma, Vaccine, vaccine

Dogs receiving various treatments are helping medicine find new therapies for people, too

December 2, 2011

When her black Lab, Emmy, started limping in 2008, Kathi Streeter suspected the normal aches and pains of aging. Then came the devastating diagnosis: osteosarcoma, a deadly bone tumor. Osteosarcoma affects humans, too—mostly children, whose long-term survival rate, if the cancer spreads, is under 40 percent. Though Emmy died in May at the ripe old age of 13, she gained nearly three years of healthy living, and one day her treatment may help those kids.

[Learn more about how dogs help mankind in Mysteries of Science: Amazing Animals.]

In her quest to save Emmy, Streeter learned about a study underway at Colorado State University’s Animal Cancer Center in Fort Collins, about 100 miles from her home in Franktown, Colo. It was testing a gene therapy that could be injected straight into osteosarcoma tumors. The gene delivers a molecule designed to induce the cancer cells to self-destruct. Veterinarians there wanted to see how well dogs reacted to the treatment, as part of an effort to determine whether it might also be investigated for use in children.

Streeter is a cancer survivor herself—in 2004, she underwent a double mastectomy and chemotherapy to treat breast cancer—and didn’t hesitate to sign Emmy up. After the injection, CSU vets gave Emmy the standard treatment, too: amputation of her leg plus six rounds of chemo. They’re now evaluating how the injection affected the tumor. Although the results of this trial have not yet been published, previous trials suggest that the therapy may enhance the immune system’s ability to combat the tumor.

CSU is one of 20 participants in the Comparative Oncology Trials Consortium (COTC), a growing program started in 2003 and managed by the National Cancer Institute to study cancer in dogs and to recruit them for clinical trials of new treatments. The goal is more effective, more personalized treatments for man as well as his best friend. “Several tumor types in dogs mimic human cancers in their biologic behavior and genetic signature,” says Susan Lana, associate professor of clinical oncology at CSU. “Dogs can help us try to answer questions like, ‘Why does this cancer spread?’ and ‘Are there genetic pathways we can explore for treatment?’ ”

Dogs are ideal models, Lana says, because they’re genetically similar to humans and share the same environment. They develop cancer naturally, unlike mice and rats, which must be engineered to have the disease. And dogs are big enough to undergo MRIs as well as blood tests and biopsies, so scientists can better observe changes in the cancer over time. Thanks to advances in genomics and gene sequencing, researchers have established which canine cancers are most similar to their human counterparts. Besides osteosarcoma, they include prostate and breast cancer, melanoma, soft tissue sarcoma, and non-Hodgkin’s lymphoma.

Vaccine success. Comparative oncology has already produced some success stories. In 2010, the U.S. Department of Agriculture approved Oncept, a therapeutic vaccine for dogs with melanoma. Therapeutic vaccines are designed to mobilize the immune system to make antibodies against cancer cells, which ideally then destroy the cells and keep the cancer from coming back, and they’ve long been the holy grail of cancer drug development. But many of the vaccines tested have proved disappointing. If Oncept is any indication, dogs might hold the key to fine-tuning cancer vaccines. Some dogs in the Oncept trials lived more than a year after their diagnosis—far outpacing the typical lifespan of one to five months with conventional therapies.

The data from the dog trials were impressive enough to prompt the Food and Drug Administration to green-light a small human trial of a similar drug. Jedd Wolchok, a physician at Memorial Sloan-Kettering Cancer Center in New York and the drug’s codeveloper, is hoping a pharmaceutical company will fund the large clinical trials that would be needed to get the human version of the vaccine approved. “These trials can take over five years and they’re exorbitantly expensive, but the risk could lead to a long-term payoff,” he says.

Veterinarian Gerald Post learned the benefits of canine cancer trials as a pet owner. “Instead of living three months, he lived 2½ years,” Post says of his miniature schnauzer, Smokey, a participant in the Oncept trials. “He taught me to leave no stone unturned.” Post is now an investigator for several canine clinical trials, which he runs out of his Norwalk, Conn., office.

Joining a trial offers twin rewards for dog owners: access to cutting-edge treatments they might not otherwise be able to find or afford, and, even when there’s little hope, the satisfaction of contributing to the quest for cures. “We knew the trial wouldn’t resolve the cancer,” says Richard Liscinsky, whose golden retriever, Samantha, 6, was part of a one-week trial of a protein-based lymphoma drug designed to restrict the growth of cancer cells. Liscinsky and his wife, Ann, who live in Bronxville, N.Y., hoped the treatment regimen would offer up some answers and give them one more summer in Vermont with their beloved pet. Lymphoma is all too common in golden retrievers; Samantha is the second of the three goldens the Liscinskys have owned that has contracted the disease. “It’s frightening that cancer is so rampant—for all of us,” Ann says.

Owners who participate in trials typically get at least part of the care at no charge. The funding comes from a variety of sources, including federal grants, pharmaceutical companies, and philanthropists with a soft spot for dogs. Among the last group are Dave and LuAnn Runkle of Wayzata, Minn., who lost their golden retriever, William, to a rare and aggressive form of cancer called histiocytosis and then launched the Will-Power Cancer Research Fund to support comparative oncology trials at the University of Minnesota. The $10,000 they’ve raised so far is helping to fund trials in both dogs and cats, which also develop tumors that are similar to human cancers. Dave’s motto? “Help your animal, help yourself,” he says.

Shelter rescues. Some comparative oncology programs are reaching out to dogs that have no owners to rely on. In the summer of 2009, the University of Pennsylvania’s School of Veterinary Medicine launched the Shelter Canine Mammary Tumor Program, for example. Veterinarians there rescue dogs with mammary tumors from shelters, remove the tumors, and then adopt the dogs out to local families. More than 30 dogs have benefited so far, says Karin Sorenmo, Penn Vet’s chief of medical oncology.

Sorenmo’s team is studying the tumors to try to figure out what causes benign breast cells to turn malignant and spread. “It’s metastasis that kills the cancer patient,” Sorenmo says. “If we can learn what genetic events make tumors spread, it opens up a lot of possibilities for new treatments.”

For Mildred Edmond, that possibility is intriguing on several levels. Edmond adopted Cali, a 6-year-old bichon frise in the Penn trial who had 11 tumors removed. “Poor little Cali—she had a full mastectomy,” Edmond says. Edmond herself survived breast cancer six years ago, so she is eager for the scientists at Penn to unravel the complexities of the disease. “I have two granddaughters and a great granddaughter. I’d hate for them to go through what I went through,” she says. (Edmond and Cali are both now cancer-free.)

Dog survivors sometimes play more than a research role. After Emmy survived her bout with cancer, Streeter signed her up for a program at Children’s Hospital of Denver called YAPS, for Youth and Pet Survivors. With Streeter’s help, Emmy sent letters and photos to a young girl being treated for brain cancer. “I became [the patient's] pen pal,” Streeter says. “She brought pictures of Emmy to surgery.”

Streeter likes to think that giving Emmy the opportunity to contribute to a fuller understanding of a cancer that affects kids made the disease more bearable for everyone involved. Emmy loved children, she says. “If I could have asked her permission to do the trial, she would have said, ‘Yeah, let’s do it.’ ”

Arlene Weintraub is the New York editor of Xconomy.com.

This story is excerpted from Amazing Animals, a U.S. News & World Report special edition. You can order it at www.usnews.com/animalsbook or by calling 1-800-836-6397.

Veterinary oncology chief named chairman of small animal clinical sciences

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Posted 05 Jul 2011 — by James Street
Category Cat osteosarcoma, Dog Osteosarcoma, genetic, vaccine
Filed under Announcements, InsideUF (Campus), Top Stories on Tuesday, July 5, 2011.

GAINESVILLE, Fla. — Rowan Milner, the Hill’s Associate Professor of Oncology at the University of Florida College of Veterinary Medicine, has been named the new chairman of the college’s department of small animal clinical sciences following a national search.

Milner, who also serves as chief of the oncology service for the UF Veterinary Hospitals, will succeed Colin Burrows in the position following Burrows’ retirement after nearly 30 years of service. Milner’s appointment was effective July 1.

“As chair, Dr. Milner will assume overall responsibilities for faculty recruitment, mentoring and promotion,” said Glen Hoffsis, the college’s dean. “He will also be responsible for budget management, leadership in research and veterinary and graduate student education.”

Milner will work closely with the hospital’s chief of staff to continue provide high-quality clinical service to the nearly 20,000 small animal patients that are treated annually at UF.

“Dr. Milner also will work with the scientific community of the Health Science Center, practicing veterinarians from Florida and other constituents of the college and our hospital,” Hoffsis said.

Dually board-certified in veterinary internal medicine and veterinary oncology, Milner received his early academic training from the University of Pretoria in South Africa. His research interests include osteosarcoma, melanoma vaccine, stereotactic radiosurgery, targeted radiotherapy and tumor suppressor genes.

He joined UF’s faculty in 2001 and has twice received Clinician of the Year awards from UF veterinary students. In recognition of his development of a promising new melanoma vaccine and for other research, Milner was named Clinical Researcher of the Year by the Florida Kennel Club in 2007. In 2011, he won the Pfizer Award for Research Excellence and in 2009 he received a faculty enhancement opportunity award from the Office of the Provost at UF.

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Contact
Sarah Carey, careysk@ufl.edu, 352-294-4242

Dr. Patrick Moore explains cancer-causing viruses to Laureate Society

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Posted 05 Dec 2010 — by James Street
Category Immune System, Vaccine, vaccine, Vaccine Studies, virus studies
By Carolyn SusmanSpecial to the Daily News

Updated: 8:46 p.m. Saturday, Dec. 4, 2010

Posted: 6:07 p.m. Saturday, Dec. 4, 2010

Dr. Patrick Moore looked out at the people dining with him at Café Boulud and delivered a shocking statement. He had been talking about a virus that causes a rare skin tumor: “About everybody in this room is infected with it,” he said.

Those enjoying the luncheon for the American Cancer Society’s Laureate Society took note.

The “it” he was referring to is the Merkel cell polyomavirus, which was discovered in his lab at the University of Pittsburgh in 2008 and causes most Merkel cell carcinomas.

But he told everyone to relax. Although this virus is common, the skin cancer tumors that are caused by it are “relatively rare.” He thought it would be of interest to this group of Cancer Society supporters, he said, because factors such as aging, sun exposure and immune suppression are key to the tumor development.

The more widely known skin cancer, melanoma, is much more common, but the Merkel cell carcinoma, he said, is “far more dangerous.”

Moore, together with his wife, Dr. Yuan Chang, is responsible for discovering the viral causes of four human cancers. Among them, and perhaps best known among their work, was identifying and isolating, in 1994, the Kaposi’s sarcoma-associated herpesvirus, which causes this epidemic cancer among HIV/AIDS patients.

He and his wife focus their research on the link between viruses and cancer, a link that was considered tenuous, he said, until very recently.

“Until you know the cause, your hands are tied,” he said. “Otherwise, it’s ‘Katy bar the door.’” Meaning, he said, it’s full speed ahead when that piece of the puzzle falls into place.

He mentioned that, all told, there are seven viruses — “all very different in their behavior” — that cause human cancers. The human papillomavirus (HPV) is one of them. The most common sexually transmitted virus in the United States, according the Centers for Disease Control, HPV is a cause of cervical cancer, as well as several other genital cancers.

Several women in the audience were interested in why the newly available vaccine against this virus is recommended only for young people.

Moore explained that these vaccines are preventive, but the virus — which usually resolves on its own in adults — is already there in many adults once they are sexually active.

Advaxis receives USPTO patent for Listeria vaccine

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Posted 23 Nov 2010 — by James Street
Category Dog Osteosarcoma, vaccine

The U.S. Patent and Trademark Office has approved Advaxis, Inc., (OTCBB: ADXS), the live, attenuated Listeria monocytogenes (Listeria) immunotherapy company, intellectual property protection to patent application 11/223,945 – a live, attenuated Listeriavaccine that secretes novel fragments of the tumor antigen HER2/neu (human epidermal growth factor receptor 2), when using the company’s proprietary listeriolysin O (LLO) fusion platform technology. The patent also extends protection to LLO-HER2/neu proteins independent of live Listeria which can be used as protein vaccines.

“This patent will be Advaxis’ 29th in its growing intellectual property portfolio”

The HER2/neu antigens are incorporated in a construct that is planned for use in a canine osteosarcoma study later this year and human studies in breast and braincancer in 2011.

“This patent will be Advaxis’ 29th in its growing intellectual property portfolio,” said Advaxis EVP of Science and Operations Dr. John Rothman. “When combined with our 43 pending applications, the company believes it to be the most comprehensive portfolio in the bacterial immunotherapy space today. Our IP protection is designed to support the successful commercialization and further scientific development of our platform technology. The expansion and vigorous protection of Advaxis’ IP portfolio is one of our key company strategies.”

Source : Advaxis

Source: http://www.news-medical.net/news/20100909/Advaxis-receives-USPTO-patent-for-Listeria-vaccine.aspx