Thursday, June 21, 2018
Health

A new way to attack cancer lives inside the shark. But where? (w/video)

SARASOTA — Scientist Carl Luer has spent most of his life studying an animal humans inherently fear: sharks.

The predators of the sea have been the villains of thriller tales since the 1974 novel, Jaws They’ve invaded the streets of Los Angeles in the cult classic Sharknado movies.

But Luer, a senior researcher at Mote Marine Laboratory and Aquarium in Sarasota, discovered they have more to offer than farfetched story lines. Sharks, it turns out, could hold the key to a promising new cancer treatment in humans.

A potential cure lies somewhere in the shark’s immune system. And after 39 years of working with sharks and their close relatives, skates and sting rays, Luer believes researchers finally may be close to finding it.

They have tried for decades to link the shark’s incredible ability to heal wounds and its fast-acting immune system to human healing. But for Luer, who is also the lab’s founding director of biomedical research, it has been the work of his life.

From a small off-shore laboratory on picturesque Lido Key, he’s one of a few researchers across the globe who have studied the cancer treatment link, and likely for the longest. At almost 70, he hopes he can push his research to the next level — potentially in clinical trials — before he retires or hands it over to the next generation of scientists.

It won’t be easy.

For the past 15 years, Luer and his research partner, Catherine Walsh, have struggled to find the grant funding needed to keep the research alive, and progress has stalled.

"I thought it would have happened by now," Luer says. "But no one has gotten any further than we have."

• • •

Sharks have body part not found in any other species. It’s called an epigonal organ, which is connected to the ovaries or the testes. And it’s where they get their immune cells.

"For a century, it had been thought that sharks didn’t get cancer. This was purely anecdotal, of course," Luer said. "Now, there are maybe 15 documented cases in literature where sharks showed signs of cancer, instances where the tumors they presented were not malignant."

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That was enough evidence for Luer to want to explore further. So in the 1980s, he began to look deeper at the immune system of sharks to try to find out why they had such low rates of cancer.

That led to early tests in which Luer injected powerful carcinogens into sharks to see if they would produce cancer, like they always did in other animals. They never did.

Around that time, Walsh joined him as a postdoctoral scientist, and they drew on her experience studying immunology in cattle. "What we learned is that this organ that is unique to sharks, skates and stingrays looked and functioned just like bone marrow in humans," Luer said.

So he and Walsh went to work trying to grow immune cells cultured from sharks so they could study them. It took a year and a half to figure out how to keep them alive in a lab environment because no one had done it before. By the late 1990s, Walsh and Luer were filtering a substance the shark immune cells secreted and adding them to human cancer cells.

"The first time we did it, it killed the cancer cells," Luer said plainly.

So they tried it again. And again, until they’d mixed 15 types of human cancer tumor cells, from prostate to breast cancer, with what came from immune cells harvested from the shark’s epigonal organ.

"There are a lot of things that kill cancer cells," like chemotherapy and radiation, which are among the most widely used therapies today, Luer said. "But they also kill normal cells."

In contrast, what the shark cells produced was killing the cancer, but not attacking the healthy cells.

"It was very dramatic and we were very optimistic," Luer recalls. "But we had the cart before the horse."

• • •

There’s not a scientist, physician, neighbor or parent of a local little league baseball player that would describe Luer as anything other than kind and "just a nice guy."

For Jim Gelsleichter, an associate professor who studies sharks at the University of North Florida in Jacksonville, Luer has been a mentor, friend, and the inspiration behind why he wanted to be a marine researcher.

"I met Carl when I was still an undergrad at Eckerd College," he said. "He had lectured there and I was so impressed. It was my first time I met a scientist that was so down to earth and kind rather than stuffy and business-like or all science-oriented. He made a big impression on me as a young scientist."

Gelsleichter would go on to work with Luer at Mote for 10 years. There he’d watch Luer’s research progress.

"Carl is a very detail-oriented scientist. This work he’s been doing has taken a while, but that’s kind of an association of his character," he said. "He moves slowly because he wants to be sure. We should all be like that. He takes his time to develop these projects, to test all possible hypotheses. That doesn’t lend itself to a quick turn around."

Luer and Walsh were working on sharks and cancer cells at a time when other researchers were experimenting directly with shark cartilage. Combined with the growing and lucrative shark-fin soup market in the late 1980s, the news of sharks’ healing capacities created a media storm.

"Shark populations plummeted at that time, largely because of fisheries for food like shark fin soup, but this was a big point at the time," Gelsleichter said. "The interest in shark cartilage contributed to the population loss. People were taking cartilage pills, even though there was no science to prove they worked."

Despite the negative consequences, it helped drive funding and media attention to the work Luer and Walsh were doing at Mote Marine, including a grant from the National Cancer Institute in 2004. It also gave Mote a platform for conservation. Sharks and skates were used for test subjects, but Luer learned to maintain a line of animals in captivity instead of plucking them from the wild.

He also hopes to find a way to grow the shark immune-system cells in a lab without having to continuously harvest them from sharks. Luer says he uses eight to 10 sharks a year as test subjects, specifically bonnetheads, which are local and plentiful in Southwest Florida.

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The interest in sharks at the time also led to a collaboration with Tampa’s Moffitt Cancer Center, a partnership that Luer hoped would push the research over a hurdle that had stalled their progress for nearly 15 years. While Luer and Walsh had discovered that the immune cells were able to attack the cancer, they couldn’t pinpoint just what it was the cells were producing that triggered that kind of response.

"We knew that it was a protein, but we don’t know which one," Luer said.

In the early 2000s, physicians and researchers at Moffitt were investigating how the immune system played a role in controlling cancer. The work eventually led to breakthroughs like Chimeric Antigen Receptor Therapy, or "CAR-T" cell therapy, which was approved for some cancer patients by the U.S. Food and Drug Administration last year. CAR-T uses white blood cells from the patient’s immune system and re-engineers them in a lab to target and wipe out cancer cells.

Dr. Clay Smith, who worked at Moffitt at the time, was fascinated by the work Luer was doing just down the road in Sarasota.

"I knew nothing about shark biology other than I like scuba diving with them," said Smith, now the program director of the Blood Cancer & BMT Program at the University of Colorado. "What I learned is that sharks’ immune and blood systems are different from humans, but not all that different as you would expect for an animal that’s been around for hundreds of millions of years."

Sharks have similar types of white blood cells and lymph nodes as humans, he explained.

In the collaboration with Moffitt, Luer and Walsh would continue to cultivate the shark immune cells. Then a team of Moffitt researchers would take that material and test it on cancer cells in their labs in Tampa.

"The very stuff produced by these immune cells was very dramatic in killing cancer cells," Smith said.

But the work never got too far. Smith took a job in Vancouver, and the funding that kept it going dried up before they could pinpoint what triggered the response. "It was more of side project," Smith said.

Luer says that he and Walsh have made progress since, and the research is very much alive. But they are still trying to answer the same question: Which protein is it?

The research can’t progress to any clinical trial without knowing how and what makes the cells work in this way. Researchers can’t synthesize it either without this information, which means it can’t be produced for human consumption or testing.

But Smith says Luer’s work is a long way away from that.

"It’s not crazy to think this could work," he said. "But it will require a lot of very structured, disciplined work to make sure it’s safe."

• • •

Back at Mote, Luer and Walsh chip away at shark research in the crowded upstairs laboratories while families and tourists wander the halls of the public aquarium below them. Some of Luer’s skate subjects are on view behind glass on the ground floor. A worn photo of a young Luer, with a moustache, hiked shorts and long socks, is pinned on a droning refrigerator near a row of test tubes.

Luer and Walsh have other projects, too. Luer also has studied the mucus on skates and stingrays for wound healing and potential antibiotic properties, work that has generated grants from the Department of Defense and other sources over the years.

The most recent interest in their shark and cancer work came in 2015, when Luer and Walsh worked with a research team at the University of Central Florida through a grant challenge from a local private foundation. The partnership included Sun BioPharma and Northern Capital Partners, and was aimed at drug development. UCF researchers tested whether the shark cells remained potent after shipping on dry ice, thawing and being re-dissolved in liquid.

While Luer and Walsh were named finalists for the grant and received $25,000 for their work, they did not win the $375,000 award to pursue it further. Luer said he’s still trying to find more funding with UCF.

"There’s a bevy of folks trying to develop anti-cancer stuff. Every drug company in the world wants to get their hands on that," said George H. Burgess, director emeritus of the Florida Program for Shark Research at the University of Florida. "But their work is kept quiet because of company secrets. Meanwhile, Carl does it the old-fashioned way. He’s an open book, publishing what he’s finding and what works — and what doesn’t — every step of that way."

Burgess, who has known Luer since he started working at Mote in the 70s, said scientists’ constant quest for funding is the "sad truth" of the research world these days.

"The reality is, to get science done, you have to get the money to support it," he said. "While we don’t want to be beholden to someone else, the fact of the matter is, you have to have someone support what you do to do your stuff. In Carl’s case, he has to constantly look for funding to produce the next steps. And from a medical standpoint, he damn well has to have it right."

It’s a fairly common dilemma among scientists, Burgess said.

"It’s not uncommon to get into a situation where there’s a big hurdle you have to get over. You keep chipping away it, hoping you find your way over it," he said. "We all want to find the answer, but sometimes that’s not going to be solved in our lifetime. We produce our part of the jigsaw puzzle as best as we can, and leave that last piece to be found by someone else."

Contact Justine Griffin at [email protected] or (727) 893-8467. Follow @SunBizGriffin.

 
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