Army surgeon on track to head off cancer before it starts

By Rob McIlvaineApril 19, 2012

Dr. Peoples Scrubs Up
1 / 3 Show Caption + Hide Caption – (Photo Credit: U.S. Army) VIEW ORIGINAL
Surgery in Honduras
2 / 3 Show Caption + Hide Caption – Honduran Dr. Jose Mejia, left, and Col. George Peoples, Mobile Surgical Team, work together to perform surgery on a Honduran boy March 15, 2012, at Santa Teresa Hospital in Comayagua, Honduras. The seven-member Mobile Surgical Team travels around Hon... (Photo Credit: U.S. Army) VIEW ORIGINAL
Peoples discusses vaccine trial
3 / 3 Show Caption + Hide Caption – Col. George E. Peoples explains how cancer vaccines help to combat breast cancer during an interview at San Antonio Military Medical Center. Peoples, director and principal investigator for the Cancer Vaccine Development Program, has helped to develo... (Photo Credit: U.S. Army) VIEW ORIGINAL

WASHINGTON (Army News Service, April 18, 2012) -- 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 DEVELOPMENT

The current vaccine is the result of nearly 20 years of research by Peoples and others, and has paralleled the development of the drug Herceptin.

"Herceptin is one of our biggest breast cancer drugs right now. It targets a protein commonly over-expressed in breast cancer cells called human epidermal growth factor receptor 2, or HER2/neu," Peoples said.

This drug, he said, has cut the rate of breast cancer recurrence in half ; the first drug to ever have this dramatic of a response.

"So of course, HER2/neu became the molecule of the decade and Herceptin now is a multi-billion dollar drug," Peoples said.

At the time that this was all being developed in the 90s, he said, HER2/neu had also been identified as a potential target for vaccination at two different labs.

"During my surgical residency in Boston, I was working with a lab at the Harvard Medical School in the Laboratory of Biologic Cancer Therapy, and there was another lab working on a very similar type approach at MD Anderson Cancer Center at the University of Texas," he said.

After identifying the protein HER2/neu as a potential target, both labs continued their search for the portion actually recognized by the immune system. The immune system knows HER2/neu is a dangerous protein, particularly during adult development, and if it sees a lot of this protein, it will kill that cell, Peoples said.

The E75 peptide was discovered at MD Anderson by Dr. Constantin Ioannides and his then-graduate student Bryan Fisk. Interestingly, Bryan would later become an Army physician, Peoples related.

"But then, as luck would have it, after I finished my surgical residency in Boston, I did my surgical oncology fellowship at MD Anderson," Peoples said, adding that he shifted his focus to this peptide, working in the lab with Dr. Ioannides and helping initially with one of the first clinical trials, run by Dr. James L. Murray, a medical oncologist there.

After finishing his fellowship, Peoples went back to Walter Reed to start as staff surgical oncologist where he initiated a similar clinical trial of E75, but focused on using the vaccine to prevent the recurrence of cancer.

During this time, he did vaccine trials on multiple HER2/neu-related peptides and other antigens, which he says work well for breast cancer, but also other similar-type proteins made by cancers that can be targeted as cancer vaccines.

VACCINE MIGHT PREVENT OTHER CANCERS

"People who are in my field approach this by saying, yes there are ways to treat cancer, but why wait and treat, why not try to prevent?

The desire to prevent disease, he 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 HER2/neu is the majority of cancers actually express some levels of the protein. It's not exclusive to breast cancer, either, Peoples said.

"Clinically, we think about it mostly being associated with breast cancer, but that's just because of the popularity of Herceptin," he said.

Unfortunately, Peoples said, Herceptin is not effective in most cancers. In fact, in breast cancer only 20 percent have a sufficient amount of the HER2/neu protein for the antibody to work, and in other cancers it's even less than that.

"So that leaves the other 80 percent of breast cancer out and not eligible for Herceptin," Peoples said. He added that fortunately, the NeuVax vaccine can target breast cancers that have lower levels of HER2/neu expression.

Along with the 20 percent of breast cancer that has high enough levels of HER2/neu for Herceptin to work, Peoples further explained that another 20 percent of breast cancer has no HER2/neu expression.

"But then there's that middle 60 percent that has some level and that's actually the group of people we're primarily targeting with the vaccine right now, because we've shown that the vaccine works well in that group and that group has no Herceptin-like treatment right now," Peoples explained.

"Probably the bigger point there is ... if it works, if the vaccine works in that lower level of HER2/neu expression group, then you can go look at other cancers that are not being targeted by Herceptin..."

And those other cancers, he said, are anything that comes from an epithelial cell, which are the big cancers - lung cancer, prostate cancer, colon cancer, some blood cancers, ovarian cancer, and gastric cancer.

"So it's all of the big cancers that we face in the United States, all of those have a significant proportion of the tumors expressing some level of HER2/neu and, therefore, theoretically targetable by the vaccine.

"So that's the more exciting piece to this. We have tested the vaccine in prostate cancer, we're testing it currently in ovarian and endometrial cancer, we have not done lung or colon, yet, though that's on the list for future trials.

"So we have tried to show that the vaccine can, in fact, be used in multiple cancers, and it's more related to HER2/neu expression than it is to the actual name on the tumor," 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.

HER2/neu, he said, is an important antigen, but it may not be the most critical antigen. There may be others, particularly ones that are common in the development process of the cancer.

"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. So if you have immunity against one of those proteins, we'll use HER2/neu for an example, if you had immunity against HER2/neu, then you could prevent the development of any one of these types of cancers. 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.

Related Links:

Army.mil: Health News

STAND-TO!: 235 Years of Army Medicine: Bringing Value... Inspiring Trust

Brooke Army Medical Center

Centers for Disease Control and Prevention

MD Anderson Cancer Center