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Harnessing The Immune System To Fight Cancer

February 9, 2015

When Barbara Marder was diagnosed with lung cancer three years ago, she had part of her right lung removed, went through a round of chemotherapy and tried to move on with her life.

"I had hoped that everything was fine — that I would not create difficulty for my children; that I would get to see my grandchildren grow up," says Marder, 73, of Arnold, Md.

But a routine scan a year later found bad news: The cancer was back — this time in her other lung.

"I was very disappointed," says Marder. She knew her prognosis was grim. "I decided at that point that … I should think about the fact that perhaps this was going to advance rapidly at this point. And check and make sure: 'Is my will in order? What should I do so that my children aren't left with a mess to clean up in my house?' "

But Marder didn't give up. She started exploring her options, which eventually brought her to Johns Hopkins in Baltimore, where doctors are testing a new type of cancer treatment known as immunotherapy.

"Immunotherapy for cancer means developing treatments to harness your immune system and using your own immune system to fight the cancer," says Dr. Julie Brahmer, an associate professor of oncology and Marder's doctor.

Scientists have been trying to do this for decades. After all, our immune systems can fight off all kinds of health threats. So, why not cancer? But nothing seemed to really work.

"It's been very frustrating," Brahmer says.

But scientists recently discovered that cancer takes a page from Harry Potter: It puts on a kind of invisibility cloak.

"Cancer can keep the immune system from recognizing that it's bad and keep it from attacking itself," Brahmer says.

Now scientists have found a way around this.

"The breakthrough is in therapies called 'checkpoint inhibitors,'" Brahmer says.

Checkpoint inhibitors are drugs that pull off cancer's invisibility cloak by blocking the switch that turns it on.

"It prevents that invisibility cloak or that force field or shield … from going up," Brahmer says. "So it can't shield itself from the immune system."

And these drugs seem to be working, at least for some patients — melting away the toughest tumors, such as some melanomas, the deadliest kind of skin cancer.

"They seem to be working quite well for multiple different cancers," Brahmer says, including kidney cancer, bladder cancer, head and neck cancer, lymphoma and even perhaps breast and lung cancer.

So Marder volunteered for one of Brahmer's studies testing a checkpoint inhibitor called nivolumab, or Opdivo, for lung cancer. Within weeks of starting her infusions, the tumors in her left lung began to disappear.

"That was very, very exciting. It really changed my perspective. I thought, 'Jeepers,' " Marder says.

Checkpoint inhibitors can cause serious side effects when the immune system attacks healthy cells, causing dangerous, even sometimes life-threatening, organ damage. But so far that appears to be relatively rare.

Most patients just get a little tired. Some, like Marder, get an itchy rash. But compared to traditional chemotherapy, it's easier in most cases.

"You can live a great life," Brahmer says. "Travel and try to live your life as as normally as possible. That's definitely different than chemotherapy."

One big question is, how long will these drugs keep working? Traditional chemotherapy often stops working with time — the length of effectiveness varies depending on the patient, the type of cancer and the stage at which it was diagnosed. But so far checkpoint inhibitors seem to keep going a lot longer, even in patients who have stopped responding to standard chemotherapy. No one knows yet how much longer.

But Brahmer says so far it looks promising.

"We're reporting three-year survival rates in (lung cancer) patients who we would say typically should not be around," Brahmer says.

For melanoma, researchers have followed patients for even longer, she says.

When Marder came back for a checkup more than a year after starting her treatment there was still no sign of her cancer. Marder was thrilled.

"I'm very fortunate," she says.

But another big question about these drugs is how much they cost — more than $120,000 for each round. That's drawn some intense criticism.

"Cancer immunotherapy is the most exciting thing we have going on in the field," says Dr. Peter Bach, director of the Center for Health Policy and Outcomes at the Memorial Sloan Kettering Cancer Center in New York. "It's frustrating that the companies are gauging the U.S. system with their prices."

The companies that make checkpoint inhibitors defend their price tags and say they will help make sure patients can afford them.

"Any patient who needs access to a checkpoint inhibitor made by Bristol Myers Squibb will have access through a robust patient-assistance program," says Michael Giordano, who heads oncology drug development at the company.

Brahmer hopes doctors will figure out a way to cut the costs and says patients may not have to stay on the drugs indefinitely. That's because when patients stop taking the them, immune system cells known as T-cells seem to remember how to keep the body cancer-free.

"We think that over time your immune system creates memory," Brahmer says.

The T-cells remember how to attack the tumor and stop the cancer from putting up a shield. "So those T-cells continually keep that cancer under control. Even without treatment," Brahmer says.

Brahmer might try that for Marder. But for now, she's coming back every two weeks to receive infusions and because she is in a study, Marder doesn't have to pay for the drug.

Brahmer knows she and other researchers will have to treat a lot more patients for a lot longer to really know just how well these checkpoint inhibitors work. and for how long. Many scientists suspect it will take a combination of checkpoint inhibitors to get the most out of our immune systems to fight cancer.

"We're trying to figure out how to personalize this treatment," Brahmer says. "Who needs just one checkpoint inhibitor? Who needs a combination to really unleash the immune system? That's where this is probably headed."

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