Central Mass. Scientists Chip Away At Finding Cancer Cures
PHOTO/Matt Pilon
Eric von Hofe, left, of Antigen Express, said a clinical trial for the firm's vaccine to stop breast cancer from reoccurring is “very promising.”
Dr. Giles Whalen of UMass Medical School: “The translation of these technologies out of the lab and into human trials is a fairly expensive proposition.”
Life sciences companies and researchers in Central Massachusetts go to work each day looking for new ways to treat many diseases.
But no disease has drawn more attention and funding than cancer. Though treatments, detection and knowledge of cancers have improved, a cure — and even ways to reasonably manage certain cancers — remains elusive.
That's despite more than $6 billion per year in federal research grants and countless venture capital investments in pharmaceutical and biotech companies.
Cancer kills 1,583 people every year in Worcester County, which has a slightly higher-than-average cancer rate compared to other parts of the state, according to data from the National Vital Statistics System and the National Cancer Institute that cover 2005 through 2009.
But the work marches onward. UMass Medical School is involved in more than 20 clinical trials related to cancer, and several companies in the area are also researching and pursuing treatments, looking for ways to starve the disease of vital proteins — which has become a core approach in researching remedies for the spread of cancer throughout the body — and for clues to help them better understand the body's genetic language, which is uniquely intertwined with how the disease operates.
The following efforts represent three research and development efforts in cancer therapies in the region.
Attacking From All Angles
Cancer is a broad term, encompassing cell growth that impacts different parts of the body with varying effects. Some cancers are easier to treat than others. And some offer little hope for recovery.
That's the case for pancreatic cancer, in which only one in five patients survives a year after diagnosis.
That's part of the reason why Brian Lewis, an associate professor in molecular biology at UMass Medical School, has studied pancreatic cancer for 15 years.
"This was an important health question that needed better answers," he said.
His studies have determined that a gene known as KRAS often mutates early in the development of a pancreatic tumor, and that KRAS seems to rely heavily on a protein called insulin-like growth factor receptor (IGF1R).
Other researchers have tried to target those proteins, with mixed results.
Lewis suspects the solution lies in targeting the right mix of proteins at the right time.
So, UMass has licensed a number of compounds from pharmaceutical companies that Lewis is using to try to find combinations that seem to impact tumor growth. He has found that attacking IGF1R and another protein simultaneously makes the cancer cells sensitive to a chemotherapy drug called gemcitabine.
He compares the effort to the drug cocktail that emerged to treat HIV.
But before he can think about a clinical trial, Lewis needs to prove his theories in animal models. He hopes to enter a Phase I trial (the first step in proving a drug's worth) within two years.
Besides the complex research, one hurdle that lies ahead is negotiating with the companies from which UMass is licensing the compounds Lewis wants to use. Licensing for research is one thing, but he anticipates it will get more complicated in trying to go into trials.
Another challenge that all cancer researchers face is financial, he said.
"In this golden age, where technology has really shifted, we can do all these fantastic things, but there's a second side to that coin in that all these technologies are expensive."
Tricking The Immune System
Antigen Express, housed in Worcester's biotechnology park, is working on a vaccine to stop the reoccurrence of breast cancer for chemotherapy patients.
Akin to the way a flu vaccine uses flu particles to trick the immune system into attacking the virus, Antigen's leading biological drug candidate, AE37, aims to "convince" the body that it needs to attack cancer cells, explained Eric von Hofe, CEO of Antigen.
"That's a tricky thing to do, because cancer cells arise from the body's own tissues," and the immune system doesn't like to go after its own cells, von Hofe said.
The approach is known as immunotherapy. The vaccine is in the later stages of a Phase II trial with the U.S. Food and Drug Administration (FDA).
The trial is taking place at 14 sites, mostly in North America. Antigen expects to report more data from the trial in October, von Hofe said. He described previously released initial data as "very promising."
Antigen has chosen to focus on breast cancer for now, partly because of the economics of drug trials. It's possible that AE37 could vaccinate not just against recurrence of breast cancer, but also the formation of other types of types of cancers. However, proving to the FDA that such a "prophylactic" vaccine is safe and actually works would be extremely expensive, von Hofe said. The company would have to give the vaccine to thousands of patients, then wait years for results. Focusing only on breast cancer for now makes the trial feasible, he said.
"What we'd like to do first is just get this out there on the market, and find a way of showing a benefit," he said. "Then you think of expanding it."
Antigen and its Canadian parent company, Generex, hope AE37 could offer treatment options to breast cancer patients for whom the drug Herceptin may not be an option.
Both drugs target a protein that is common in breast cancer. While Herceptin works well on patients who display high levels of that protein, von Hofe said, Antigen's drug contains a modified fragment of the protein that makes the immune system "see" it better, and it may actually work better with patients with lower levels of the protein.
Count Dr. Giles Whalen among the researchers trying to crack cancer through helping the body to better recognize malfunctioning cells.
Whalen, a professor of surgical oncology at UMass Medical School who is also a practicing surgeon and interim director of the school's cancer center of excellence, thinks injecting a particular antigen directly into tumors could help the human body recognize the cancer cells as threats and attack them, including those that have spread in the bloodstream to other parts of the body.
Giles and his research team, which includes UMass professor Uri Galili, are nearing the end of a phase I trial to test the safety of the treatment.
"The entire animal kingdom has this (antigen) on their cells, except old world primates like us, gorillas, chimps, orangutans and the like," Whalen said. "So when our immune system sees cells with this market on it, we have the highest number of antibodies directed against that in our system."
It's the same reason the human body would reject a transplanted pig kidney or some other organ because of foreign antigens, he added.
So far, Whalen's team has shown the idea can work in mice, and the phase I trial has thus far shown the injections don't have harmful side effects.
Whereas other approaches seek to identify and isolate certain proteins that affect cancer cell growth, Whalen said his team's approach has certain elegance.
"You don't have to find or isolate anything," he said. "You just inject it into the tumor."
The next step is to show that the injections can have the same immunological response in humans as they've had in mice.
As FDA trials progress into the subsequent phases, they get bigger and more expensive.
Whalen said UMass has partnered with a Boston-area company, which is licensing the UMass technology to provide some needed capital for the effort, particularly as the federal National Institutes of Health seeks to dial down some of its funding because of budget sequestration.
"The translation of these technologies out of the lab and into human trials is a fairly expensive proposition," Whalen said.
The second phase of the Whalen's trial would likely focus on colon cancer because it's common, produces large tumors and is easily injectable. But Whalen has also studied melanoma and is not ruling out going after other types of cancer in in the future.
Many immunotherapy treatments have had spotty success. Some have worked well for some patients but failed entirely for others. Whalen said scientists are still trying to understand why certain patients react differently to treatments.
Whalen is well aware of the past, but hopeful about the future of his trial.
"It could really work," he said. "It may not, but if it turns out, it'll be huge."
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