Medical Device Daily National Editor

What's better – to invent or to innovate?

Invention, of course, can get you into the history books, though inventors often miss out on the value of the resultant products.

Innovation, by contrast, is considerably easier because you can use available technologies – and get more quickly to market – and to the clinic, importantly, in the case of medicine.

Taking available technologies and putting them together in a sophisticated new way is the strategy being employed by David Mooney, PhD, and a group of bioengineers and medical collaborators at Harvard University (Cambridge, Massachusetts).

They are using polymers commonly employed in device technology, combining these with standard approved drugs, to develop a new pathway for the delivery of vaccines and, they hope, further out, for reengineering the human immune system against diseases.

In his lab, Mooney and his team used biodegradable polymers similar to those used in sutures and other materials to create small discs (about 8.5 mm across) that are implanted beneath the skin – similar to contraceptives that are implanted in a woman's arm.

The implants are about 90% air and somewhat comparable to a sponge, he told Medical Device Daily. The discs incorporate drugs and antigens which interact with the cellular physiology of the body to attack cells that may develop into tumors.

Implanted in rats for this study, the strategy destroyed an aggressive form of melanoma – a form that would kill the rodents in 25 days, the researchers said – in 90% of the rats. And they said this approach could turn out to offer the most effective strategy for delivering a cancer vaccines.

"We purposely took things [for the study] that all had an established safety record in humans," Mooney told MDD, rather than inventing. "We took some standard pieces and put them together."

He said also that the system can be used with drugs already in general use and that the primary challenge in the method is "to get the drug to recognize the type of cancer."

The approach of this research is to manipulate the cells already in the body as opposed to a method that Mooney said has been attempted without great success.

Previous work on cancer vaccines, he said, has focused on removing immune cells from the body and reprogramming them to attack malignant tissues. The altered cells are then re-injected into the body.

Theoretically and according to the evidence supporting this approach, he said, this should work. But he noted that the work utilizing this technique has shown that more than 90% of the re-injected cells die before having any effect.

By manipulating the cells already within the body, as in this study, the strategy also may be usable for boosting the body's immune system to fight off other diseases, Mooney said. And the focus of the team's research is more on a preventive approach rather than on exploring the therapeutic pathway versus diseases already attacking the body.

"We've been very interested for a number of years in cell therapies in the context of regeneration," he said. "But we began to think, a couple of years ago, that it would be greatly preferable if we could control cells that already existed within the bodies instead of transplanting cells."

The transplantation process, he called "awkward and expensive," and that it is "much nicer do all the manipulation in the body."

Further explaining the approach, Mooney said that the drugs and cytokines bioengineered into the discs act to attract "immune-system messengers" called dendritic cells. The dendritic cells then report to nearby lymph nodes, "where they activate the immune system's T cells to hunt down and kill tumor cells throughout the body."

In essence, he said that the discs are used to "mimic the danger ... that activate these cells. They know they've seen something foreign so that travel to the lymph nodes ... and go find the tumor" and destroy it.

While Mooney's group focuses on creating the discs, he emphasized the important collaboration with medical school researchers at Harvard, citing especially the work of Glenn Dranoff MD, of the Dana-Farber Cancer Institute (Boston). Researchers there, he said, developed some of the cancer vaccines in clinical trials ... and provided a tremendous amount of assistance in term of the immunological aspect."

The next steps for this research?

The collaborators will continue to study this approach, Mooney said, and, in the meantime, a parent is being sought and the method has been licensed to InCytu (Lincoln, Rhode Island), which he described as "a small startup company."

As with all of the basic research approach, Mooney told MDD it is "very hard to predict" when the method will reach general use for patients.

But he said that the attempt was to 'take an approach where that, hopefully, would not be too long. All the components of this system are routinely used in patients today, and all the components have safety profiles that are very good."

Based on "the way we combine things," Mooney said, the hope is to move the method "quickly to the clinic."

Mooney and his Harvard colleagues describe the research in the current issue of the journal Nature Materials.

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