- The Washington Times - Wednesday, December 9, 2009

Scientists are finding new ways of killing cancer tumors by using specially treated implants to destroy malignant cells inside the body — a method of treatment that, if broadly successful, has the potential to replace invasive surgery and dangerous chemotherapy and radiation treatments.

One such method, developed by researchers at Harvard University, employs bioengineered disks treated with cancer-fighting proteins that attack an existing tumor directly at the site and reprogram the body’s immune system to produce more of these antigens on its own.

According to a paper last month in the journal Science Translational Medicine by David J. Mooney and Dr. Glenn Dranoff, the treatment protected 90 percent of mice from a skin cancer that was injected into them and that usually kills the animals in 25 days.

This trial is the first case of success involving an implanted cancer vaccine and mammals, though long-term effects and risks remain unknown.

“If we vaccinate mice first and then introduce cancer cells into mice, 90 percent never get cancer,” Mr. Mooney told The Washington Times. “When we introduced tumors into the mice first, they [slowed the cancer growth] about 50 percent of the time.”

Human clinical trials are expected to begin “in about a year,” said Mr. Mooney, a Harvard professor of bioengineering, who called the ability to trim established tumors “really exciting.”

The technique could represent a major breakthrough because most cancers can be treated only with surgery, chemotherapy and radiation — which also frequently kill healthy surrounding tissue and are known to have severe side effects.

Mr. Mooney compares his group’s approach to the common practice of implanting timed-release contraceptives into a woman’s arm.

Unlike vaccines against pathogens, which are intended to prevent illnesses such as polio or smallpox, antigens against cancer normally are effective only after the disease has been found.

This study showed effects closer to those of a true vaccine, which has its greatest effect before the body becomes ill. No human cancer vaccine exists, but scientists are testing the means to create one.

Two commercial vaccines on the market — Gardasil and Cervarix — are given by injection to protect against the human papillomavirus associated with the development of cervical cancer and some other conditions.

The paper by Mr. Mooney and Dr. Dranoff, an immunologist with the Harvard-affiliated Dana-Farber Cancer Institute, also compared previous efforts to develop a vaccine that involved taking immune cells out of the body, treated them with an antigen and then reinjected the immune cells into body tissues. This approach is less successful because too many of the treated cells die along the way, Mr. Mooney said.

The new approach uses biodegradable fingernail-sized plastic disks implanted into the body to attack the problem. The disks — similar in composition to surgical sutures — are filled with tumor-specific antigens that stimulate the immune system to produce T-cells programmed to fight the cancer.

Its significance goes beyond an attempt to treat only cancer, said Dr. Peter Polverini, dean of the University of Michigan Dental School.

“Imagine a material that can send instructional cues to a diabetic to produce insulin on demand,” Dr. Polverini said.

He suggested that it could be a major improvement for diabetics, who are required to get their insulin artificially through injections or an insulin pump. “The inert stuff could be anyplace, even in a dental transplant — anywhere you can stimulate the flow of saliva. It could release chemicals to stop asthma, for example.”

Long-lasting effects, including side effects, still need to be studied, he said.

Dr. Polverini’s special interest has been oral cancer, which is usually in its later stages when diagnosed. By that time, surgical therapy that involves disfigurement is often necessary.

“The tissue engineering research is more than proof of principle,” he said. “They showed it can get to work and literally get a tumor to disappear.”

Dr. Bart Kamen, medical director for the Leukemia & Lymphoma Society, said that “mice don’t mean anything to me until we can do it in people.” But he agreed that the technique “sounds like a way of making vaccine work better.”

Dr. Kamen said recent medical conferences on cancer suggest that “vaccines are the current wave and the wave of future. Our goal is to make the body be able to react against the tumor better.”

Dr. John Marshall, a medical oncologist who is director of developmental therapeutics at the Georgetown Lombardi Comprehensive Cancer Center, was skeptical of the Harvard study’s long-term impact. He said the implant offers “a new method of delivery, but the concept is not that fresh.”

Dr. Marshall said the true barrier for a cancer vaccine is reprogramming the immune system to attack only cancerous cells, not how one delivers antigens.

“We have been curing mice with vaccines for a long time, so that is not, in my opinion, news. The vehicle may be better than what we have had before in this particular kind of cancer, but it depends on the kind they put into the mouse,” he said. “The trick is how you reprogram the immune system.”

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