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When cancer can’t escape

If we were to present her research as an action movie plot, this is how Kate Rittenhouse-Olson and her team at the University at Buffalo plan to beat cancer:

A SWAT team of engineered antibodies hunts down cancer tumors where they live, secures the perimeter so they can’t escape and then busts down the door and delivers a fatal dose of chemicals to finish the job, with no civilian casualties.

In a few years, this show could be playing in patients everywhere.

The most difficult part – that of the antibodies – is already filled. They were discovered – actually created – by Rittenhouse-Olson in her lab nearly 20 years ago, by cloning a mouse spleen cell with a mouse tumor cell.

“It got its immortality from the tumor cell and the antibody from the mouse spleen cell,” she explains, keeping it simple.

She named the new antibody JAA-F11. That sounds like a fighter jet that shoots down tumors, but this microbiologist is more sentimental. She made the name from the initials of her three children, Jennifer, Anna and Andrew, combined with the grid location – F11 – in the culture plate where the antibody grew.

After her initial discovery, she has worked with students and her longtime research lab technician Susan Morey to reproduce the antibody and test its ability to stop cancer in its tracks, using mice as live subjects and human cells in Petri dishes. Now, they are “humanizing” the antibody, taking the mouse antibody binding ability and attaching it to human antibody molecules.

JAA-F11 bonds with the part of the cancer cell – a sugar, the Thomsen-Friedenreich antigen – that helps it move through the bloodstream. Once JAA-F11 attaches, the antigen doesn’t work and the cancer doesn’t spread.

It has proven to be remarkably effective.

Now, JAA-F11 is taking its first major steps in front of a wider audience. Rittenhouse-Olson has started a company to develop a marketable cancer therapy and already has early interest from several major pharmaceutical companies.

She has been awarded hundreds of thousands of dollars from the National Cancer Institute and University at Buffalo to begin the next phase of testing on her breakthrough, which is a few steps ahead of human trials.

“We aren’t all the way there, but it shows real promise,” Rittenhouse-Olson said.

A sister’s tribute

The personal implications for Rittenhouse-Olson go far beyond the fact that JAA-F11 eventually could make her quite rich.

If the therapy works in humans with anything close to the 80 percent effectiveness rate that she is seeing now in the lab, it will fulfill a promise she made to her sister and to herself.

In 1986, her sister, Robin Quataert, died of breast cancer. She was 31.

“I was 24 when she was first diagnosed,” Rittenhouse-Olson said. “The cancer had not spread to the lymph nodes, so her prognosis at first was pretty good. … Four and a half years later, the cancer was back. She died soon after that.”

Rittenhouse-Olson was a graduate student at UB when her sister became ill, and was already preparing for a career in cancer research. Losing Robin provided more incentive to succeed.

Looking back, Rittenhouse-Olson says her sister likely had a subtype of breast cancer now known as “triple-negative,” which is more prevalent in young women and one of the most stubborn types to treat. That makes it even more exciting for her that the JAA-F11 antibody seems to work on triple-negative tumors, at least in the lab.

No surprise, then, that she decided to name her fledgling company “For-Robin.”

Down to business

Becoming a pharmaceutical entrepreneur was not part of her original plan. Rittenhouse-Olson is first and foremost a scientist, and after that a well-regarded professor. She is director of UB’s Biotechnology Undergraduate Program and its biotech internship program, and logs her share of time in the classroom and teaching lab. Last year, she and her colleague Ernesto De Nardin published a textbook, “Contemporary Clinical Immunology and Serology,” for which she drew the original diagrams for many of its illustrations of molecules.

“I love to teach, and I’m a very visual person,” she said. “I think it really helps the students if they can see how these molecules work together.”

Even at home, science takes center stage. Her husband is James R. Olson, director of the Department of Pharmacology and Toxicology at UB – and the future toxicologist of For-Robin. A blended family, they have seven grown children between them and one grandchild.

“One son did say, ‘You know we don’t talk about the kind of things at dinner that other people do, right?’ ” Rittenhouse-Olson conceded. “We do like our work, and we do like to talk about it.”

Stopping by her small office in Cary Hall one morning, James Olson admitted his wife’s new venture has required some adjustments for the two academics.

“There’s no way faculty really want to go into business,” Olson said. “We are not ‘business’ people.”

But in this case, they felt For-Robin would be their best chance to put the research to work.

“It’s a new part of life,” Rittenhouse-Olson said. “If I didn’t spin off my own company, I would retire, and I would have cured a lot of mice, and I’ll never know what else we could have done.”

Not flying solo

UB has been behind her all the way, she said, a continuation of the nurturing environment she has enjoyed since her years there as an undergrad and Ph.D. candidate.

“Buffalo was special, even then,” she said.

After earning her master’s at the University of Kentucky, where she was the only woman in her program, she was glad to return for her doctorate to UB, where classes were about equal numbers men and women.

“I found myself in an area where women and men were treated the same – and it is one of the best immunology programs in the country,” she said.

Doing post-doctorate work at Roswell Park Cancer Institute, she chose to study the relationship of carbs – in this case, molecular sugars – and cancer.

“When people think ‘carbohydrates,’ they think, oh, ‘potatoes.’ But they are building blocks for so many things,” she said. “I thought, they can be an important target for my antibody.”

The specificity of her antibody in targeting a carb like the Thomsen-Friedenreich antigen avoids the “collateral damage” of traditional chemotherapy and radiation treatment, which began as a sort of “carpet bombing” approach to cancer eradication. As with other newer cancer treatments, JAA-F11 aims only at the tumor, leaving normal cells untouched.

That’s what the evidence shows so far, and, as far as UB’s economic development office is concerned, that’s enough to help For-Robin get off the ground.

“There’s an entrepreneurial ecosystem here to help people like Kate – business development programs specifically to help grow private sector jobs in the life sciences,” said Marnie LaVigne, associate vice president for economic development at UB.

Her office decides if it is worth spending the money to patent a discovery, as it did with JAA-F11, then assists with paperwork, a business model and making important connections.

“We help them learn to act like a business and talk like a business,” LaVigne said.

They also help with money. Curing cancer is expensive, and if they want to speed up and expand their research, it will take lots of it. Rittenhouse-Olson’s antibodies live in high-tech plastic containers in a climate controlled cabinet – it looks kind of like a dorm fridge, but is much more expensive – and they dine on a special medium that costs a few hundred dollars per liter.

And, as lab tech Morey said, “There’s a lot of consumables involved. We could keep a small plastics industry going.”

The National Cancer Institute provided more than $280,000 in May, and UB added to that. For-Robin has $30,400 from the UB Center for Advanced Biomedical and Bioengineering Technology and $50,000 from UB’s Bruce Holm Memorial Catalyst Fund.

“This is quite different from basic research funding from federal sources,” said Jeffrey Dunbar, director of UB’s STOR office. “We call this ‘gap funding,’ to get them from research to development for the private marketplace.”

Previously, Dunbar said, universities didn’t have to find money for this because pharmaceutical companies would fund even early phases of testing.

“Now they let the big universities take on the risk to see if it’s viable,” he said. “Then big pharma, with its deep pockets, will fund the very expensive Phase III human trials.”

Moving forward

For-Robin has a busy few years ahead. Rittenhouse-Olson believes an optimistic timeline would put her therapy on the market in about five years. She and her colleagues are doing more data collection now and then will move on to testing the drug in dogs, whose tumors are much like those in humans. So much so that it could have veterinary uses, too, at some point, she said.

Then, if the money is available, they will begin clinical trials with cancer patients. Starting with small doses at first, to make sure there are no unexpected side effects, they would increase dosage and, Rittenhouse-Olson says, probably also try adding toxins to her antibody.

“It’s perfect for carrying a drug into a cell,” she said, with some excitement slipping through her scientific calm.

If it all works as hoped, JAA-F11 could eventually be used to treat other cancers, too – prostate, colon and lung cancers, for starters.

However, she’s a pragmatic person, and Rittenhouse-Olson does not want to get ahead of herself.

“We’ve been on this roller coaster before,” she said, referring to earlier research and funding hopes – but she also is not someone who quits easily.

She is at heart an optimist.

“You have doubts sometimes, but you work through it,” she said. “The first thing always is to do no harm, but we do really believe this will be as good for people as it has been for mice.”