Unmasking Cancer ; Immune System Helped to Recognize Tumors

SOUTH BEND — Arising from our own cells, cancer tumors are largely invisible to the body’s natural defenses.

Cancer thrives by avoiding detection by the immune system’s many sentinel cells, cells which easily recognize viruses, bacteria and other foreign invaders.

Because cancer cells look very much like our normal, home-grown cells, they slip past the radar, according to Dr. Michael Method, a gynecological oncologist and surgeon in South Bend.

“Cancer is part of self,” Method said. “The body gets confused. Is that part of me, or not?”

Researchers, however, are finding ways to unleash the immune system’s potent army of killer cells against cancer.

Method is one of two local physicians who are on the front lines of this endeavor.

He has treated about two dozen local patients with an experimental medicine intended to uncloak ovarian cancer cells in order to make them visible, and vulnerable, to the immune system.

The innovative approach being used by Method involves what are called “monoclonal antibodies.”

These molecules are similar to the antibodies that the immune system produces in vast numbers when it is stimulated by recognition of a foreign invader. The big difference is that monoclonal antibodies are bioengineered in a lab, using mouse cells, and infused into the patient intravenously.

New forms of treatment

The other local physician involved in immunotherapy research is Dr. Douglas Schwartzentruber, medical director for the Center for Cancer Care of Goshen Health System. He is working with a different cancer and a different approach.

While Method is applying monoclonal antibodies to ovarian cancer, Schwartzentruber is investigating a combination of two immunotherapies against skin cancer that has become advanced and spread to other organs of the body.

Schwartzentruber is protocol chairman for a national clinical trial to determine if interleukin-2, itself a form of immunotherapy already proven effective against melanoma, works better if it is combined with a cancer vaccine. The combination treatments are being given at 17 centers around the country but are not yet available to patients in Goshen, although they soon may be.

Researchers are looking for new approaches to cancer treatment because many forms of the disease, despite decades of costly effort, still defy the conventional techniques of surgery, chemotherapy and radiation.

As a surgeon and specialist in gynecological cancers, Method has seen how advanced ovarian cancer usually returns even when surgery and chemotherapy have succeeded in putting the disease into complete remission.

In fact, recurrence of ovarian cancer is the norm for women who are diagnosed in a late stage of the disease, as nearly 80 percent of them are.

It recurs within five years 80 percent of the time, even after primary treatments have eliminated all signs of tumors detectable by X-rays, blood tests and clinical exam, Method told local physicians during a recent talk at Memorial Hospital.

In 70 percent of women in this category, the heart-breaking return of cancer occurs within two years, Method told the doctors at Memorial.

How can this happen when all tests seem to have shown that the cancer is gone?

“They still have the disease; we just can’t see it,” Method said. “That’s why we need something else. The individual has to kill the last cell themselves.”

Finishing the job

That something else, he believes, is an immunotherapy that can unmask leftover cancer cells and expose them to the body’s immune system, allowing it to finish the job.

Method, who has been working with monoclonal antibodies for 12 years, said they are given in such low doses that the treatment has virtually no side effects.

That’s good news because women who receive this treatment have already endured a painful surgery and a grueling round of chemotherapy.

“We’ve beaten these patients down,” he said.

The compound being used by Method goes by the brand-name OvaRex. It is being privately funded through venture capital. Method, however, said he has no financial stake in the business.

OvaRex works by targeting a particular protein found on the surface of the ovarian cancer cell.

The medicine attaches itself to those cancer cells but doesn’t kill them. Instead, it has a “tail” that calls in some of the immune system’s killer cells. The tail is like a big flag saying “Here’s the enemy!”

The first tests of OvaRex, unfortunately, did not show an improvement. So the researchers took a closer look at the data and found that a subset of patients — those whose cancer had gone into complete remission — did benefit from a significant delay in recurrence; instead of recurrence occurring in 10 months, it happened after an average of 24 months.

So a new study is now under way involving only patients who respond fully to primary therapy. It will take about nine months for everyone enrolled in the trial to complete their treatment and then another 18 months of monitoring to determine if survival has improved, he said. That means, at best, OvaRex won’t win FDA approval for two to three years, Method said.

Reducing recurrence

Method said he foresees the day when cancer is targeted with not just one antibody, but with three or four. That will, in effect, create a louder shout alerting the immune system to the growing danger posed by the cancer.

He also believes monoclonal antibodies will be shown to work against other common cancers that put a patient at high risk of recurrence after successful primary treatment. Those include cancers of the breast, colon and skin.

Current conventional treatments for advanced ovarian cancer succeed in extending life, and even people in late stages can benefit, Method emphasizes. But they provide a complete cure and long-term survival only about 15 percent of the time.

“If we could get that up to 30 percent or 50 percent, that would be huge,” he said.

Schwartzentruber, a cancer surgeon and tumor immunologist, also has years of experience working with immunotherapy.

Before returning to his native Goshen last year, Schwartzentruber served for 16 years as an investigator at the prestigious National Cancer Institute’s Surgery Branch in Bethesda, Md., where he specialized in immunotherapy.

He explained that interleukin-2 is one of a handful of immunotherapies already proven to have some effect against cancer.

In fact, interleukin-2, which is offered at the cancer center in Goshen, is actually one of the proteins, called cytokines, that immune cells use to communicate with one another.

Giving a person a dose of interleukin-2 stimulates the production of disease-fighting T cells, Schwartzentruber said.

Then the experimental vaccine that Schwartzentruber is working with primes those T cells to recognize and attack metastasized skin cancer cells.

“So you build your army with interleukin-2,” he said. “The vaccine trains your army.”

Interleukin-2 alone rarely produces complete remission or a cure against advanced melanoma, Schwartzentruber said, where large tumors have appeared. The statistics are, in fact, perhaps even more bleak than they are for ovarian cancer.

“It’s only a small minority, 7 percent to 9 percent (whose cancer goes into complete remission after treatment with interleukin-2 alone),” he said.

But in a previous trial of the vaccine, the response rate (including partial response) to the combination of interleukin-2 and vaccine was double that of interleukin-2 alone, he said.

“Vaccines are not very powerful alone against cancer,” Schwartzentruber said. “But they may be an important part of the package.”

The effort to marshal the body’s own resources against cancer is yielding promising results, results which may be the difference between cure and recurrence for people with advanced disease.

Staff writer David Rumbach:

drumbach@sbtinfo.com

(574) 235-6358