Stopping Cancer Before It Starts

An Army doctor has helped develop a vaccine that he believes will prevent cancer, or at least its recurrence.

The drug NeuVax began phase III clinical trials Jan. 20, which Col. George Peoples said could lead to its Food and Drug Administration, or FDA, approval. Peoples is chief of surgical oncology at the San Antonio Military Medical Center when he’s not traveling the world to provide surgical expertise or working to try and find a cure for cancer.

He is currently deployed to Honduras.

The phase III clinical trial for NeuVax will involve at least 700 breast cancer patients at 100 sites in the United States and abroad. The trial is titled PRESENT, Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment.

Participants will receive one intradermal injection every month for six months, followed by a booster inoculation every six months thereafter. The primary endpoint is disease-free survival at three years.

 “The first patient was vaccinated with NeuVax in January at San Antonio Military Medical Center, Fort Sam Houston, Texas,” Peoples said.

Peoples is the director and principal investigator for a Cancer Vaccine Development Program that he has been working on since the early 90s. The vaccine carries the generic name E75.

This third and final phase of testing before FDA approval will bring NeuVax one step closer to the market and to the breast cancer patients who need more options, Peoples said.

According to the Centers for Disease Control and Prevention, about 203,000 individuals in the United States are diagnosed with invasive breast cancer each year.

VACCINE MIGHT PREVENT OTHER CANCERS

Yes, there are ways to treat cancer, but why wait and treat, why not try to prevent? The desire to prevent disease, Peoples said, is what led to the eradication of smallpox and hopefully will lead to the eradication of polio.

“If you vaccinate enough people, you prevent the disease and it can no longer exist in the population; eventually it’s eradicated. So, if you believe that concept, then we need to figure out a way to prevent cancers, as opposed to detect them earlier or treat them better,” Peoples said.

He said one of the advantages of the new drug is the majority of cancers actually express some levels of the protein. It’s not exclusive to breast cancer, either, Peoples said.

TRULY PREVENTIVE VACCINE

A lot of times, he said, people actually do have cancer cells, or “cancer-esque” cells. It’s just they haven’t formed the cancer yet. And so those cells will theoretically be recognizable to the immune system, and can be affected by a vaccine.

“Ultimately, that is the goal – to provide a protective-type vaccine so that a person never actually develops the cancer,” Peoples said.

“So you could ultimately envision a vaccine that targets those critical proteins that are necessary for cancer to form. And if you have immunity, such that your body can recognize those proteins as soon as they show up, then theoretically, you could prevent a person from ever developing a cancer.”

“The good news is, I think those proteins are likely to be common proteins, shared among multiple cancer types,” he said.  “So, it wouldn’t be a cancer-specific vaccine, but a vaccine that would protect you against lung cancer, colon cancer, prostate cancer, etc.”

“I think that is theoretically possible, it’s just a matter of identifying the most useful antigens to target,” Peoples said.

By Rob McIlvaine, www.army.mil.

Military’s Groundbreaking Vaccine Targets Breast Cancer

By Elaine Sanchez for American Forces Press Service

Military researchers here have developed a cutting-edge cancer vaccine that’s slashing breast cancer recurrence rates and giving some survivors a better shot at a cancer-free future.

After more than a decade of research and testing, the cancer vaccine, dubbed E-75, soon will move on to its final phase of testing to earn Food and Drug Administration approval, said Army Col. (Dr.) George E. Peoples, director and principal investigator for the Cancer Vaccine Development Program at San Antonio Military Medical Center in Texas.

The team has high hopes for this vaccine and its lifesaving potential for breast cancer survivors, particularly since breast cancer is the most prevalent type of cancer seen among military beneficiaries in the hospital here, said Peoples, who also serves as the deputy director of the U.S. Military Cancer Institute and the medical center’s chief of surgical oncology.

“We’ve made a commitment to take care of active-duty personnel, spouses and retirees,” the colonel said. “And cancer is a notable problem among beneficiaries.”

The vaccine, Peoples explained, targets a protein commonly over-expressed in breast cancer cells called human epidermal growth factor receptor 2, or HER2/neu.

Cancer vaccines typically target some protein or antigen expressed on cancer cells, he noted. “The idea is to train the immune system to recognize that protein or piece of protein that’s highly expressed on cancer cells, but not on normal cells,” he said. “That way the immune system can differentiate what’s abnormal and normal. If the immune system can recognize it, it marks it for death, basically.”

The cancer vaccine concept has been around for a long time, Peoples noted, but the team here has adopted a different approach to test their effectiveness. The vast majority of vaccines in the past were tested on end-stage cancer patients, he explained. However, a vaccine is meant to stimulate the immune system, and a healthy immune system isn’t typically seen in someone in the last stages of cancer.

As a result, “a lot of early cancer vaccines tested … in end-stage patients were found not to be helpful,” Peoples said. “No real surprise there.”

 To more appropriately gauge the vaccine’s effectiveness, Peoples’ team decided to test it among patients who have a healthy immune system — cancer survivors who are disease-free but at risk for recurrence. Experts can predict recurrence based on several factors including family history, age, size of tumor and the presence of involved lymph nodes, among other indicators.

The researchers targeted the HER2/neu protein, which is expressed at varying levels in women with breast cancer, then honed in on the 60 percent of women who express the protein at low to intermediate levels. The vaccine is a mix of the E-75 peptide of the HER2 protein and an immune system stimulant.

They started with a 200-patient trial in 2001 and followed each woman for five years. Half of the women received the vaccine — one injection a month for six months — and the other half was the control group.

The outcome was very promising, Peoples noted. The recurrence rate among the women in the control group was 20 percent, and 10 percent among the women who received the vaccine. “We cut recurrence in half,” he said.

This success led to the next phase of testing, the colonel said, which will begin early this year and involve 700 to 1,000 patients.

Unlike the earlier phases, however, this step will be undertaken by a commercial company, Galena Biopharma, which has the resources and manpower to undertake such a large-scale test. The company will seek FDA approval and, if received, release the vaccine for public use.

 This phase will take about five years to complete — two years to enroll, then a three-year observation period, Peoples said.

 “The end point is the recurrence rate after three years,” he explained.

Meanwhile, Peoples and his team will turn their attention to a multitude of other projects, many based on the same concept that made the E-75 vaccine so successful — using the body’s own immune system to destroy cancer cells.

They’ve already taken the same vaccine and completed a trial with prostate cancer survivors. As with ovarian and lung cancer, prostate cancer also expresses the HER2 protein.

Peoples said he’s also intrigued by a successful trial they conducted on breast cancer survivors who express the HER2 protein at the highest levels, rather than the low to intermediate levels they focused on before. In this study, they combined their vaccine with the drug Herceptin.

They conducted a small trial with 60 women, Peoples said, and when they administered the vaccine and Herceptin together, the recurrence rate dropped to zero. “The preliminary data is very exciting,” he said. “But we need to wait and do larger trials.”

Word has spread of the cancer vaccine program’s successes and intriguing results. Military and civilian experts have approached Peoples wanting to take part in research that has such a potentially widespread impact. The idea of active, specific immunotherapy — engaging the body’s immune system to do the work of fighting the cancer — is an exciting and rapidly evolving area, Peoples explained.

Garnering this interest, Peoples has steadily built a worldwide network of military and civilian hospitals that can assist with clinical trials and research. The network includes just about every major military hospital alongside a civilian hospital in cities across the nation and overseas.

 The partnership has reached Athens, Greece, and is about to extend into Malaysia. “We’re about to circle the globe,” he said.

 Peoples attributed much of the program’s successes to this military-civilian network. “We’re very fortunate to have great partners,” he said.

 He also praised the military men and women willing to take part in the trials. They enter into them knowing they may be part of the control group that doesn’t receive a potentially lifesaving vaccine. Despite that fact, he hasn’t seen a shortage of willing participants, Peoples said.

“The military is an ideal setting for clinical trials,” he said. Service members, retirees and family members have a strong sense of service, he noted. “They want to be involved and contribute to the research,” he added.

While they’re focusing on secondary cancer prevention, the ultimate goal, Peoples noted, is primary prevention, meaning cancer prevention among people with a predicted risk of cancer based on family history and genetic markers.

“Hopefully, sometime in my lifetime we’ll figure that out,” he said.

Breakthrough in Early Cancer Detection

A simple cheek swab could show early signs of lung cancer

Cape Cod-TV correspondent Melissa Chartrand went into the hospital three years ago to undergo a hysterectomy, a common procedure that was supposed to eliminate her abdominal pains. But for Melissa, a far more serious pain was just beginning.

"I went in for a hysterectomy and when I woke up, they told me I had ovarian cancer. Let's just say I was in total shock," recalls Chartrand. Her shock was followed by five months of intense chemotherapy for advanced ovarian cancer that put her life on hold. The five-year survival rate for her stage III diagnosis was roughly one in three. Chartrand, a mother of three, was in for the fight of her life.

With few early symptoms, ovarian cancer--like many cancers--can be hard to detect without invasive and expensive procedures. "Early detection is absolutely not only key but probably the only way for us to win the war on cancer," says Vadim Backman who is a biomedical engineer at Northwestern University in Evanston, Ill.

With support from the National Science Foundation (NSF), in part funded through the American Recovery and Reinvestment Act of 2009 (ARRA), Backman's research is shedding light on how early cancer detection can be made cheaper, more accurate and less invasive. "We're developing new optics technologies to learn about tissue structure and composition, and we are applying these technologies for early cancer screening," he says.

 The team's research is part of a field that's called bio-photonics, where light becomes an analytical tool for biology. Backman and his colleagues perfected a new type of microscopy, which they most recently demonstrated using cheek cells harvested with a small brush stroked against the inside of the mouth. When the researchers shine light on the harvested cells, photons bounce off structures within them at different angles depending on whether the cells are healthy or not.

The process is highly sensitive, able to detect even subtle abnormalities that could indicate problems elsewhere in the body. Backman is currently developing screeners for a number of cancers by harvesting cells from areas near organs that could become malignant. For example, cheek cells are harvested as a pre-screener for lung cancer, and cells harvested from just inside the rectum can be analyzed to prescreen for potential colon cancer.

Backman says both technologies are minimally invasive and can be practiced in a primary care setting. He adds that the colon screening he's testing doesn't involve the discomfort of bowel prep that, as Backman says, "Everyone loves to hate."

A slightly more invasive pre-screener takes cells from the upper intestine to screen for pancreatic cancer. The current test for pancreatic cancer involves taking a probe into ducts around the pancreas and poses a high risk of injury.

Once the harvested cells are analyzed, Backman says he can detect details previously unseen with conventional microscope technologies. "We see alterations in cells that are indicative of pre-pre cancer, if you will. If you were to take the cells under the microscope, you could not tell a difference."

A few miles from Backman's lab is Evanston Hospital. It's part of Chicago Land's NorthShore University HealthSystem. Dr. Hemant Roy is NorthShore's director of gastroenterology. He's also Backman's research partner. Roy showed us a probe that takes Backman's technology out of the lab and into practical use. The probe, which does not yet have a name, is currently used in clinical trials. It uses bio-photonics to analyze tissue inside the mouth for early lung cancer screening. It's a small, elongated, flexible flashlight, no thicker than a pencil. It shines a small light on the inside of the mouth, reads back how the light is reflected and sends the data to a computer. Roy takes a reading by simply pushing a button while shining the light on tissue inside the cheek. Raw data sampled from the light is displayed as a small graph on the computer's screen.

"With this probe, we've probably done a couple of hundred patients. We're about 90 percent accurate," says Roy. "I think if this works, we could really make a big difference in how we treat patients. We can make a huge impact on population screening." One day Backman and Roy hope that devices similar to this will be used in physical exams as routinely as taking blood pressure or using that tongue depressor to make you say "ahh."

Backman and Roy will soon be part of a new clinical trial using bio-photonics to screen cervical cells for signs of ovarian cancer. That's something Melissa Chartrand, who has been cancer-free for over two years now, can truly appreciate. "If there had been some pre-screening tool or some kind of early detection, I might not have had to go through any of what I went through," says Chartrand. "If they caught it earlier, it might have gone from stage III to hardly a stage I. Maybe I'd have no chemo or even less surgery. Imagine that."

If Backman and Roy's research is any indication, the early detection that Chartrand imagines might soon be a reality.

The research in this episode was funded by NSF through the American Recovery and Reinvestment Act of 2009.

Miles O'Brien, Science Nation Correspondent

Jon Baime, Science Nation Producer

Military’s Groundbreaking Vaccine Targets Breast Cancer

By Elaine Sanchez
American Forces Press Service

SAN ANTONIO  – Military researchers here have developed a cutting-edge cancer vaccine that’s slashing breast cancer recurrence rates and giving some survivors a better shot at a cancer-free future.

After more than a decade of research and testing, the cancer vaccine, dubbed E-75, soon will move on to its final phase of testing to earn Food and Drug Administration approval, said Army Col. (Dr.) George E. Peoples, director and principal investigator for the Cancer Vaccine Development Program at San Antonio Military Medical Center here.

The team has high hopes for this vaccine and its lifesaving potential for breast cancer survivors, particularly since breast cancer is the most prevalent type of cancer seen among military beneficiaries in the hospital here, said Peoples, who also serves as the deputy director of the U.S. Military Cancer Institute and the medical center’s chief of surgical oncology.

“We’ve made a commitment to take care of active-duty personnel, spouses and retirees,” the colonel said. “And cancer is a notable problem among beneficiaries.”

The vaccine, Peoples explained, targets a protein commonly over-expressed in breast cancer cells called human epidermal growth factor receptor 2, or HER2/neu.

Cancer vaccines typically target some protein or antigen expressed on cancer cells, he noted. “The idea is to train the immune system to recognize that protein or piece of protein that’s highly expressed on cancer cells, but not on normal cells,” he said. “That way the immune system can differentiate what’s abnormal and normal. If the immune system can recognize it, it marks it for death, basically.”

The cancer vaccine concept has been around for a long time, Peoples noted, but the team here has adopted a different approach to test their effectiveness. The vast majority of vaccines in the past were tested on end-stage cancer patients, he explained. However, a vaccine is meant to stimulate the immune system, and a healthy immune system isn’t typically seen in someone in the last stages of cancer.

As a result, “a lot of early cancer vaccines tested … in end-stage patients were found not to be helpful,” Peoples said. “No real surprise there.”

To more appropriately gauge the vaccine’s effectiveness, Peoples’ team decided to test it among patients who have a healthy immune system -- cancer survivors who are disease-free but at risk for recurrence. Experts can predict recurrence based on several factors including family history, age, size of tumor and the presence of involved lymph nodes, among other indicators.

The researchers targeted the HER2/neu protein, which is expressed at varying levels in women with breast cancer, then honed in on the 60 percent of women who express the protein at low to intermediate levels. The vaccine is a mix of the E-75 peptide of the HER2 protein and an immune system stimulant.

They started with a 200-patient trial in 2001 and followed each woman for five years. Half of the women received the vaccine -- one injection a month for six months -- and the other half was the control group.

The outcome was very promising, Peoples noted. The recurrence rate among the women in the control group was 20 percent, and 10 percent among the women who received the vaccine. “We cut recurrence in half,” he said.

This success led to the next phase of testing, the colonel said, which will begin early this year and involve 700 to 1,000 patients.

Unlike the earlier phases, however, this step will be undertaken by a commercial company, Galena Biopharma, which has the resources and manpower to undertake such a large-scale test. The company will seek FDA approval and, if received, release the vaccine for public use.

This phase will take about five years to complete -- two years to enroll, then a three-year observation period, Peoples said.

“The end point is the recurrence rate after three years,” he explained.

Meanwhile, Peoples and his team will turn their attention to a multitude of other projects, many based on the same concept that made the E-75 vaccine so successful -- using the body’s own immune system to destroy cancer cells.

They’ve already taken the same vaccine and completed a trial with prostate cancer survivors. As with ovarian and lung cancer, prostate cancer also expresses the HER2 protein.

Peoples said he’s also intrigued by a successful trial they conducted on breast cancer survivors who express the HER2 protein at the highest levels, rather than the low to intermediate levels they focused on before. In this study, they combined their vaccine with the drug Herceptin.

They conducted a small trial with 60 women, Peoples said, and when they administered the vaccine and Herceptin together, the recurrence rate dropped to zero. “The preliminary data is very exciting,” he said. “But we need to wait and do larger trials.”

Word has spread of the cancer vaccine program’s successes and intriguing results. Military and civilian experts have approached Peoples wanting to take part in research that has such a potentially widespread impact. The idea of active, specific immunotherapy -- engaging the body’s immune system to do the work of fighting the cancer -- is an exciting and rapidly evolving area, Peoples explained.

Garnering this interest, Peoples has steadily built a worldwide network of military and civilian hospitals that can assist with clinical trials and research. The network includes just about every major military hospital alongside a civilian hospital in cities across the nation and overseas.

The partnership has reached Athens, Greece, and is about to extend into Malaysia. “We’re about to circle the globe,” he said.

Peoples attributed much of the program’s successes to this military-civilian network. “We’re very fortunate to have great partners,” he said.

He also praised the military men and women willing to take part in the trials. They enter into them knowing they may be part of the control group that doesn’t receive a potentially lifesaving vaccine. Despite that fact, he hasn’t seen a shortage of willing participants, Peoples said.

“The military is an ideal setting for clinical trials,” he said.

Service members, retirees and family members have a strong sense of service, he noted. “They want to be involved and contribute to the research,” he added.

While they’re focusing on secondary cancer prevention, the ultimate goal, Peoples noted, is primary prevention, meaning cancer prevention among people with a predicted risk of cancer based on family history and genetic markers.

“Hopefully, sometime in my lifetime we’ll figure that out,” he said.

Mine-Hunting Software Helping Doctors to Identify Rare Cells in Human Cancer

By Grace Jean, Office of Naval Research Public Affairs

ARLINGTON, Va. (NNS) -- Medical researchers are demonstrating that Office of Naval Research (ONR)-funded software developed for finding and recognizing undersea mines can help doctors identify and classify cancer-related cells.

"The results are spectacular," said Dr. Larry Carin, professor at Duke University and developer of the technology. "This could be a game changer for medical research."

The problem that physicians encounter in analyzing images of human cells is surprisingly similar to the Navy's challenge of finding undersea mines.

When examining tissue samples, doctors must sift through hundreds of microscopic images containing millions of cells. To pinpoint specific cells of interest, they use an automated image analysis software toolkit called FARSIGHT, or Fluorescence Association Rules for Quantitative Insight. Funded by the National Institutes of Health (NIH) and the Defense Advanced Research Projects Agency, FARSIGHT identifies cells based upon a subset of examples initially labeled by a physician. But the resulting classifications can be erroneous because the computer applies tags based on the small sampling.

By adding ONR's active learning software algorithms, the identification of cells is more accurate and FARSIGHT's performance more consistent, researchers said. The enhanced toolkit also requires physicians to label fewer cell samples because the algorithm automatically selects the best set of examples to teach the software.

"This is not a typical Navy transition," said Carin. "But it is a transition to a very important medical tool used literally at hospitals around the world. There is a real chance this may save lives in the future."

A medical team at the University of Pennsylvania is applying the ONR algorithms, embedded into FARSIGHT, to examine tumors from kidney cancer patients. Focusing on endothelial cells that form the blood vessels that supply the tumors with oxygen and nutrients, the research could one day improve drug treatments for different types of kidney cancer, also known as renal cell carcinoma.

"With the computer program having learned to pick out an endothelial cell, we have now automated this process, and it seems to be highly accurate," said Dr. William Lee, an associate professor of medicine, hematology and oncology at the university who is leading the research effort. "We can begin to study the endothelial cells of human cancer-something that is not being done because it's so difficult and time-consuming to do."

It usually takes days, even weeks, for a pathologist to manually pick out all the endothelial cells in 100 images. The enhanced FARSIGHT toolkit can accomplish the same feat in a few hours with human accuracy.

"This is an important NIH-funded clinical study that we're supporting with FARSIGHT, and Dr. Carin's active learning system has been a great success," said Dr. Badri Roysam, an electrical and computer engineering professor at the University of Houston and program investigator for FARSIGHT.

ONR's active learning software was originally developed to allow robotic mine-hunting systems to behave more like humans when they are uncertain about how to classify an object. Using information theory, the software asks a human to provide labels for those items. This feature is valuable in mine warfare, where identifying unknown objects beneath the ocean has been accomplished traditionally by sending in divers.

"This is dangerous and is exactly what we're trying to eliminate," said Dr. Jason Stack, the program officer at ONR who funded Carin's research. "Developing unmanned systems that are not only autonomous but can also continuously learn from the warfighters employing them is core to our strategy. It speeds up mine countermeasures and helps get the man out of the minefield."

ONR provides the science and technology necessary to maintain the Navy and Marine Corps' technological advantage. Through its affiliates, ONR is a leader in science and technology with engagement in 50 states, 70 countries, 1,035 institutions of higher learning and 914 industry partners. ONR employs approximately 1,400 people, comprising uniformed, civilian and contract personnel, with additional employees at the Naval Research Lab in Washington, D.C.