Rockville Firm Wants to Give Cancer a Nanotech Poison

By Michael S. Rosenwald
Washington Post Staff Writer
Thursday, April 24, 2008

Nanoparticles are seriously small. How small? If you have hair available on your head, take a strand -- a single strand -- in your fingertips. If you line up the smallest nanoparticles side by side, you would need 10,000 of them to form the width of that strand.

Welcome to the strain-your-eyes world of nanotechnology -- the practice of taking some of the smallest particles in the world and doing something useful with them. Nanotechnology has made tennis racquets stronger. Those water-repellent pants? Thanks, nanotech.

Now, like other drug firms around the world, a Rockville biotech is ramping up efforts to use nanotechnology for making drugs. In CytImmune Sciences' case, the intent is especially audacious: Use nanoparticles of gold to target cancer tumors like a smart bomb, delivering a drug so strong that it has been known to either cause more cancer or to shut down the cardiovascular system.

Lawrence Tamarkin, the company's founder, knows what he's up against. "No company that I know of takes a drug that's knowingly toxic and knowingly severely toxic and says, 'I'm gonna try and get this approved.' I gotta tell you: Most people think I'm nuts," he said.

But there are those on both the commercial and research ends of science who say that if Tamarkin is nuts and right, the world could have a powerful new weapon against cancer. "I'd be the happiest man in the world if they can do this," said Bharat B. Aggarwal, a senior cancer researcher at M.D. Anderson Cancer Center. But it's a pretty strong if, and Aggarwal is somewhat skeptical.

Tamarkin's tale is the sort of quixotic journey that is typical in biotech, particularly in Montgomery County. He started the company 20 years ago after leaving a job at the National Institutes of Health. He used his own money. He took out a second mortgage on his house. He had two rabbits. His is a story that can end, as MedImmune's recently did, with a $15.6 billion sale to a big drug company. Or it can finish on far worse terms -- massive debt, no products -- that are spoken of in hushed voices.

Curing a mouse of cancer is one thing. It's quite another trick to be successful in humans. As Tamarkin put it, "Have you met one biotech company that can't cure mice of cancer?"

About 12 years ago, Tamarkin committed the company to using nanotechnology to deliver drugs. He wanted to resolve a common, often intractable difficulty in cancer treatment: "The problem with cancer therapies is if they are going to be effective they gotta kill all the cells. The challenge is they can't tell the good guys from the bad guys."

Tamarkin's solution is to use the gold nanoparticles as a sort of fighter jet in the body. The weapon he has chosen to load on the jet is a protein called tumor necrosis factor, or TNF, which has long been known as a potent cancer killer. The problem, according to Aggarwal, is that drug companies have largely abandoned it because it is so toxic.

If the TNF hits the cancer, fine, "But the moment it gets out it causes havoc," Aggarwal said. "TNF is a double-edge sword. One has to be very, very careful."

Tamarkin and his company, which employs 16 people, have fixed the nanoparticles so they contain a molecule that he said makes them invisible to the immune system and especially the liver and spleen, thus protecting healthy tissues. TNF has two purposes: It targets blood vessels supporting tumor growth and then destroys them. The idea is to use this treatment with traditional chemotherapy.

In conjunction with the National Cancer Institute, the company is wrapping up initial testing on 29 people. Steven Libutti, the NCI doctor overseeing the study, said he was encouraged that the testing had appeared to achieve its primary goals. One was safety. The other was to see whether the drug hit the tumors. He said there was "preliminary evidence that the drug appears to collect in the tumors."

The company is planning a larger study, in combination with chemotherapy, later this year to understand whether there are actual therapeutic benefits.

"I'm cautiously optimistic," Libutti said. "I'm hopeful this is going to be a useful addition to the weapons we have for fighting cancer."

One concern that Aggarwal has is that TNF has molecular properties that not only cause the tumors to die but also to grow. Libutti said he wasn't worried about this problem because "the lowest levels we are administering are orders of magnitude higher than the doses that could conceivably have pro-growth effects." Essentially, the tumor is being bombarded.

There is competition out there for CytImmune. GenVec, a Gaithersburg biotech, is already in final-stage testing of a TNF drug that is injected directly into tumors. There are other companies also working on highly targeted cancer treatments using nanotechnology. CytImmune, which has raised $16 million to date, needs to raise more money for the next round of testing.

The company is avoiding venture capital companies, which may be particularly leery of a TNF treatment, and targeting wealthy angel investors. Donald Kaplan, a retired financial services consultant who lives in Rockville, said he has invested several hundred thousand dollars. He did well early as an angel in the last local biotech company he invested in: Digene, which was sold for $1.6 billion last year.

"The basic concepts here are not that obtuse," he said of CytImmune. "It makes sense. At least it made sense to me." But he knows the chances of failure are great. "Investing in biotech is not like investing in a blue-chip stock. You don't buy biotech stock as part of a retirement investment strategy."

© 2008 The Washington Post Company