A Scientist's Dream Fulfilled: Harnessing The Immune System To Fight Cancer

Jun 9, 2016
Originally published on June 16, 2016 1:57 pm

Sharon Belvin's nightmare with cancer began in 2004, when she was just 22.

Belvin was an avid runner but said she suddenly found she couldn't climb the stairs without "a lot of difficulty breathing."

Eventually, after months of fruitless treatments for lung ailments like bronchitis, she was diagnosed with melanoma — a very serious skin cancer. It had already spread to her lungs, and the prognosis was grim. She had about a 50-50 chance of surviving the next six months.

"Yeah, that was the turning point of life, right there," she says.

What Belvin didn't know at the time was that a revolutionary treatment for melanoma had begun testing in clinical trials. An immunologist named Jim Allison, now at the University of Texas MD Anderson Cancer Center, had figured out that if the immune system was tweaked just right, it could do a better job of killing the cancer than the usual treatments. (Joe Palca worked for Allison early in both men's careers.)

Allison's treatment was still experimental, but if it worked, it had the potential to save Belvin's life.

"It's a new modality for treating cancer," Dr. Samuel Broder, a former director of the National Cancer Institute, says now of Allison's pioneering research. "It used to be there were three basic treatment options for cancer — surgery, radiation and chemotherapy — or some combination of those three. It's fair to say there's now a fourth option."

Allison's long search for this new kind of treatment — one that has since become a lifesaver for some cancer patients — began around a decade before Belvin got sick, when Allison was running a lab at the University of California, Berkeley.

At the time, he was what you could call a research scientist's research scientist. He was fascinated by certain powerful cells of the immune system — T cells. A subset of white blood cells, T cells travel around the body and can "protect us against just about anything," Allison says.

T cells do recognize cancer cells, but not in a way that can eliminate the disease. Allison had been studying T cells for years, and thought that by tinkering with one key molecule on the outside of these cells, he could enhance their response to cancer, enough to eradicate the illness.

He and one of his grad students ran an experiment to test the tweaked T cells on cancerous tumors in mice, and the initial results astounded them. The T cells seemed to be doing just what Allison had hoped they would do — shrink the tumors and kill the cancer.

Allison repeated the experiment with more mice over his winter break. After a few tense days, the tumors again disappeared.

"These mice were cured," Allison says.

Cancer cured?

"I've been doing this sort of stuff for years, and I'd never seen anything like that," Allison says. "And I thought, 'If we could do that in people, this is going to be amazing.' "

Allison tried to persuade drugmakers to create a human version of the treatment that had worked in mice. He thought they would jump at the chance to try a new approach.

But the biotech companies he met with didn't bite. In those days, most firms were focused on drugs that would target tumors directly, and Allison was asking them to try something very different.

"This was targeting the immune system, not the cancer," he says. "We weren't trying to kill the cancer cells. We were letting the T cells kill the cancer cells."

Thanks, but no thanks, the companies told him.

"I got very depressed," Allison says. He was sure this was the most important work of his career, but he had to get others on board.

Eventually, a scientist attending one of Allison's research talks was intrigued enough to contact a pal at the biotech firm Medarex. The company had recently developed technology that could make a human version of Allison's therapy, and was willing to give it a try.

It took a decade, but eventually Allison's big idea was ready for testing in people. A clinical trial to study the drug — now called ipilimumab, or Ippy for short — was set up at Memorial Sloan Kettering Cancer Center in New York City.

Allison decided he wanted to be part of this next chapter in the testing of immunotherapy, so he packed up his California lab and moved it to Sloan Kettering.

As it happens, Belvin was also in New York — a patient of Dr. Jedd Wolchok at Sloan Kettering. By the fall of 2004, Belvin had run through all the treatment options available to her. Nothing had worked to control the melanoma; it continued to spread dangerously throughout her body.

Belvin remembers feeling sick and depressed, and says she wasn't even paying much attention when Wolchok walked into the exam room and suggested one last treatment.

"Sharon, we have an opportunity to participate in a clinical trial here. It's something you should consider," Wolchok told her.

Belvin says she signed up without hesitation. After just four injections of Ippy across three months, her cancer was nearly gone. And at Belvin's follow-up appointment a year later, Wolchok delivered news that was hard for her to take in: "Sharon, you no longer have cancer."

And in the next breath, Belvin recalls, "he goes, 'Oh, the guy who invented this is upstairs. Do you want to meet him?' "

"Yes, of course I want to meet him!" she told her doctor.

Wolchok called Allison, who was working nearby, and told him to drop everything and come to the clinic — a part of the hospital Allison had rarely seen. Though the research scientist couldn't imagine why Wolchok was in such a rush, he quickly figured it out as he opened the door and was greeted by Belvin with a huge hug.

Belvin says she tried not to tackle him. "It was hard to control myself," she says. "I owe this man my life."

Belvin was the first recipient of the immunotherapy that Allison had ever met. "It really meant a lot," he says. "It reminded me what it's all about at the end of the day."

That was in 2005; today, Sharon Belvin is still cancer-free.

Ippy is now sold under the brand name Yervoy by Bristol-Myers Squibb, which bought Medarex in 2009.

Meanwhile, Jim Allison has become a bit of a celebrity in the cancer research world. Among other honors, he was a 2015 recipient of the prestigious Lasker Award for his achievements in medical science.

He's become well-known among patients, too. Now and again, Allison fields calls from patients yearning to learn from the master himself what it will take to cure their disease.

Allison can't really answer them. Each case is different, and using a patient's own cells to destroy tumors won't work in every patient or in every type of cancer. Still, the approach offers promise to some people that other therapies can't, and has transformed the way doctors think about cancer treatment.

It might be too early to say we're going to cure cancer, Allison says, "but we're going to cure certain types of cancers. We've got a shot at it now."

Copyright 2018 NPR. To see more, visit http://www.npr.org/.


Here's something we almost never get to say, we have a story about a cure for cancer. NPR's Joe Palca has been exploring the minds and motivations of scientists and inventors as part of his series Joe's Big Idea. Well, today, he and NPR producer Rebecca Davis bring us a story about a researcher who discovered a revolutionary way to treat cancer.

Rebecca first introduces us to a woman whose life was dramatically changed by his research.

REBECCA DAVIS, BYLINE: The woman's name is Sharon Belvin. And it's not a stretch to say that she had no desire to be part of a revolution in cancer treatment. But as it turned out, she had no choice. It was the fall of 2003 and Sharon Belvin wasn't feeling very well.

SHARON BELVIN: I was having a lot of trouble breathing even just walking up stairs to school.

DAVIS: It was weird. She was only 22 years old, a runner, but no one could find anything wrong with her. And then one day...

BELVIN: I noticed a lump growing underneath my left collarbone

DAVIS: She was terrified. Her doctor ordered a biopsy. And two weeks later, she got the results.

BELVIN: And to the shock of everybody, it came back melanoma.

DAVIS: Melanoma is an especially deadly form of skin cancer

BELVIN: I had tumors in my chest cavity and my lungs. And so it was diagnosed as stage four melanoma.

DAVIS: Sharon's prospects were grim.

BELVIN: Yeah, that was the turning point of life right there.

DAVIS: There was a good chance she wouldn't even live another six months.

JOE PALCA, BYLINE: What Sharon didn't know was there was a scientist who would be able to help, a scientist named Jim Allison.

JIM ALLISON: "Big Boss Man."


PALCA: There's nothing about Jim Allison that screams heroic cancer researcher. He's from the small town of Alice, Texas, speaks with a drawl and plays a pretty mean harmonica.


PALCA: He's also a guy who really likes to hunker down in the lab doing experiments to reveal the fundamental mechanisms of how our body's immune systems work. A decade before Sharon Belvin got sick, Jim Allison was working at the University of California, Berkeley. It was 1994. Just before Christmas, one of Jim's grad students brought him the results of an experiment they'd just finished.

ALLISON: And so he showed me this. And I just went, you know, oh, my God. You know, wow.

PALCA: The experiment was designed to treat mice with cancerous tumors. And the tumors had disappeared. The treatment wasn't like other cancer treatments. It wasn't directed at the cancer. It was directed at the mouse's own immune system, letting it deal with the cancer. Researchers had tried this approach before without real success.

But Jim had spent decades studying an immune cell called a T cell. And he figured there was one key molecule in T cells he could tweak that would let the T cells attack the cancer. Jim wanted his grad student to repeat the experiment.

ALLISON: It was right around Christmas, and he wanted to take some time off. I said, that's fine. You set up the experiment, and I'll measure the tumors.

PALCA: Some of the mice got the new treatment, others didn't. Jim didn't know which got which. He went into the lab each day over the holiday.

ALLISON: It was really depressing because I was measuring the tumors and they were not different.

PALCA: The tumors were growing in all the mice. But Jim kept checking on the mice. And then one day, he went into the lab as usual and...

ALLISON: This is interesting. Something's happening here.

PALCA: In some of the mice, the tumors started to shrink.

ALLISON: And then they shrunk all the way to nothing. And those mice were cured.

PALCA: Cured, cancer cured.

ALLISON: I've been doing this sort of stuff for years on and off. And I'd never seen anything like that. And I thought, if we can do this in people, this is going to be amazing.

PALCA: Amazing.

DAVIS: It was pretty clear that Sharon needed something amazing and fast if she was to survive the melanoma. But when she went to see Dr. Jedd Wolchok at Memorial Sloan Kettering in New York, the treatment options weren't very promising.

JEDD WOLCHOK: We treated her with chemotherapy first.

BELVIN: I had a portacath inserted. I had tubes in my chest.

WOLCHOK: Standard chemotherapy that's used for other cancers, including some of the medicines that were actually used to treat Lance Armstrong.

BELVIN: And nothing worked.

DAVIS: The cancer kept spreading into her brain. Her lungs were filling with fluid. She could hardly breathe. Dr. Wolchok had nothing left to offer her.

PALCA: Several years earlier, Jim Allison had become convinced that what worked to cure cancer in mice would work in people, too. He figured once drug makers heard about his work in mice, they'd jump at the chance to make a version of the drug that could be used in humans. But in those days, most companies were focused on drugs that would target tumors directly.

Jim's approach worked very differently.

ALLISON: This was targeting the immune system, not the cancer. It wasn't - we weren't trying to kill the cancer cells. We're trying to let the T cells kill the cancer cells.

PALCA: Jim says he kept getting the same reaction, thanks but no thanks.

ALLISON: A lot of companies expressed some interest but eventually, you know, they would say, no.

PALCA: Were there times when you're going, are you guys for real? I'm handing you...

ALLISON: No, I got very depressed.

PALCA: The most important work he'd ever done and no one would listen. But then one day, a scientist heard Jim giving a talk about his ideas for curing cancer. And that scientist was pretty sure Jim was onto something. He contacted a pal of his at a company called Medarex. Medarex had just developed a technology to make a human version of Jim's therapy and was willing to do it.

It took a decade, but eventually, the new therapy was ready for use in people.

DAVIS: Jim Allison moved his lab from California to Memorial Sloan Kettering in New York. He wanted to work closely with the scientists who were testing out the new drug. Not far from Jim's lab, Sharon Belvin sat waiting for her doctor. She was sick and depressed and she wasn't even paying attention when Dr. Wolchok came in and started talking to her.

BELVIN: He said, you know, Sharon, we have the opportunity to participate in a clinical trial here. I think it's something that you should consider.

DAVIS: She signed up and got four doses of Jim's immunotherapy, a drug now called Ipilimumab or Ippy for short. Three months after taking the new drug, Wolchok ordered a scan. And that same day, the radiologist called him with the results. Wolchok says when a radiologist calls, it's usually bad news.

WOLCHOK: But instead, this very senior radiologist who was used to, unfortunately, seeing many melanoma patients getting worse on scans, called to ask me what this young woman was treated with because the cancer is virtually gone.

DAVIS: But Sharon was so used to bad news, she didn't trust the good. When she showed up with her family to Dr. Wolchok's office for that all-important one-year follow-up, she was terrified her cancer might have returned. This time, though, the news was great. And Dr. Wolchok told her Sharon, you no longer have cancer.

BELVIN: And then in the next breath goes, oh, by the way, the man that invented this is upstairs. Do you want to meet him? How do you say no to that? Yes, of course I wanted to meet him.

ALLISON: I was in my office. And the phone rang. And it was Jedd Wolchok. He said, Jim, come down to the outpatient clinic. I said, I'm busy, you know? And he said come down here. Just come down here.

BELVIN: And, you know, he walks in the room. And I'm a very tall, 5'10'', loud Jersey girl.

ALLISON: She's very tall. And she just ran and lifted me off the ground, as I recall.

BELVIN: Did nothing but give him a hug. Kind of maybe tackled him a little bit with the hug, a little bit. I tried really hard to control myself, but it was hard.

ALLISON: And everybody started crying and hugging and everything. And I started crying. It was the first patient I'd met. And it really meant a lot. You know, it reminded me what it's all about at the end of the day.

DAVIS: That was a decade ago. And maybe you already figured this out, but Sharon Belvin is still cancer free.

PALCA: Jim Allison has become a celebrity in the cancer therapy world. He's convinced that using drugs like his that let a patient's own immune system destroy tumors is going to permanently change cancer therapy.

ALLISON: You know, it's too early to say, oh, we're going to cure cancer. But we're going to cure certain types of cancer. We've got a shot at it now.

DAVIS: I'm Rebecca Davis.

PALCA: And I'm Joe Palca, NPR News. Transcript provided by NPR, Copyright NPR.