Cancer Therapeutic Development

"Raise your hand if you haven’t been touched by cancer,” says Mylisa Parette to a roomful of strangers.

Parette, the research manager for Keystone Nano, has occasional opportunities to present her company’s technologies to business groups and wants to emphasize the scope of the problem that still confronts society. “It’s easier to see the effects of cancer when nobody raises their hand,” she says. Despite 40 years of the War on Cancer, one in two men and one in three women will be diagnosed with the disease at some point in their lifetime.

Parette and her Keystone Nano colleagues are working on a new approach to cancer treatment. The company was formed from the collaboration of two Penn State faculty members who realized that the nanoparticle research that the one was undertaking could be used to solve the drug delivery problems that the other was facing.

Mark Kester, a pharmacologist at Penn State College of Medicine in Hershey, was working with a new drug that showed real promise as a cancer therapy but that could be dangerous if injected directly into the bloodstream. Jim Adair, a materials scientist in University Park, was creating nontoxic nanoparticles that could enclose drugs that might normally be toxic or hydrophobic and were small enough to be taken up by cells.

The two combined their efforts and, licensing the resulting technology from Penn State, they joined with entrepreneur Jeff Davidson, founder of the Biotechnology Institute and the Pennsylvania Biotechnology Association, to form Keystone Nano. The new company’s first hire was Parette, whose job is to translate the lab-scale technology into something that can be ramped up to an industrial scale, and to prepare that technology for FDA approval leading to clinical trials.

Davidson, Parette, and KN’s research team work out of the Zetachron building, a long, one-story science incubator a mile from Penn State’s University Park campus. Operated by the Centre County Industrial Development Corporation, the building was originally the home of the successful Penn State spin-out company that gave it its name. A second Keystone Nano lab was recently opened in the Hershey Center for Applied Research, a biotech incubator adjacent to Penn State College of Medicine.

“Our excitement is that we think our technology has shown efficacy in a whole range of animal models,” Davidson, Keystone CEO, remarks during a recent meeting in the shared conference room at Zetachron. “We understand the method of action, the active ingredient. We think it has every chance of being useful in treating disease. Our question is, how do we push this forward from where we are today to determining, one way or another, that it really does work?”

Two approaches to drug delivery

Keystone Nano is pioneering two approaches to cancer therapy, both of which rely on advances in nanotechnology to infiltrate tumors and deliver a therapeutic agent. The approach nearest to clinical trials is a ceramide nanoliposome, or what Davidson calls a “nano fat ball around an active ingredient.” Kester, in whose lab the approach was developed, thinks of it as a basketball with a thick bilayer coating that contains 30 percent active ceramide and a hollow interior that can hold another cancer drug.

Kester is an expert on ceramide, a naturally occurring lipid, or fat molecule, that is involved with apoptosis, a type of programmed cell death. Part of the reason that cancer tumors are able to survive the body’s defenses, not to mention chemotherapy and radiation, he explains, is that the cancer can suppress ceramide activity in the tumor. The combination of a proven cancer drug, such as sorafenib, delivered in conjunction with ceramide could be a powerful approach to attacking drug-resistant tumors.

The second approach is Adair’s nanoparticles, called NanoJackets, because, Kester points out with a laugh, they are “dressed to kill.” Made from calcium phosphosilicate, a non-toxic material that is essentially the same biomaterial as teeth and bones, NanoJackets will encapsulate a variety of active pharmaceutical ingredients. They show promise both as powerful imaging agents for detecting early stage tumors, and as effective treatment for human breast cancer in animal models.

Both approaches are based on the ability to deliver toxic drugs directly to the site of a cancer tumor without the familiar off-target toxicities that plague most current cancer therapies, leading to nausea, hair loss, nerve damage, and sometimes even death. “Both of our technologies are based on non-toxic materials,” Parette emphasizes. “That gives us a significant advantage in a clinical setting.”

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