Saturday February 24, 2018

Immunotherapy : Allison’s Trials

Among other honors, Jim Allison was a 2015 recipient of the prestigious Lasker Award for his achievements in medical science

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Doctors performing Operation Image Source: Wikimedia Commons
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  • If the immune system was tweaked just right, it could do a better job of killing the cancer than the usual treatments.
  • Allison tried to persuade drug makers to create a human version of the treatment that had worked in mice.
  • Immunotherapy has transformed the way doctors think about cancer treatment.

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.

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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.”

Backbone Surgery Image Source: Wikimedia Commons
Backbone Surgery Image Source: Wikimedia Commons

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.”

Adoptive T-cell therapy Image Source- Wikimedia Commons
Adoptive T-cell therapy Image Source- Wikimedia Commons

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.”

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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.”

-by Ajay Krishna (with inputs from NPR)
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Cigars, Pipes Tied To Same Risks As Cigarettes

Traditionally, doctors have asked just whether people smoked cigarettes, but they should instead be questioning patients more broadly about tobacco use

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E-cigarettes
E-cigarettes is considered to be safer than tobacco cigarettes. Pixabay
  • Cigarettes are not the only tobacco products which can cause death
  • Other tobacco products like cigars and pipes are just harmful
  • All these tobacco products can cause cancer

Cigarettes are not the only type of tobacco products that can lead to premature death or fatalities from smoking-related cancers, a U.S. study confirms.

While people who exclusively smoke cigarettes have twice the risk of premature death from all causes compared to people who avoid tobacco altogether, exclusive cigar smokers have a 20 percent higher risk of early death, researchers report in JAMA Internal Medicine.

Cigarettes are not the only harmful tobacco products available in the market. Pixabay
Cigarettes are not the only harmful tobacco products available in the market. Pixabay

When it comes to fatalities from specific cancers that have been tied to tobacco use, cigarette smokers have four times the risk of people who never used tobacco, but cigar smokers are 61 percent more likely to die of these cancers and pipe users have 58 percent higher odds.

“We knew exclusive users of cigars and pipes were at greater risk of disease than people who do not use tobacco,” said lead study author Carol Christensen of the U.S. Food and Drug Administration’s Center for Tobacco Products. “However, this study provides information that reflects today’s patterns of tobacco use.”

Also Read: Banning E-Cigarettes Deprives Indian Smokers of a Less Harmful Alternative: Experts

These data “underscore the importance of complete quitting,” Christensen said by email.

For the study, researchers examined nationally representative survey data, collected starting in 1985, from 357,420 participants who were followed through 2011.

Overall, 203,071 people, or about 57 percent, never used tobacco at all. Another 57,251 participants were current daily cigarette smokers, while 9,414 said they had a less frequent habit and 77,773 were former cigarette smokers.

In addition, 531 people were current daily cigar smokers, while 608 individuals used cigars less frequently and 2,398 had quit.

For pipes, 1,099 participants had a current daily habit, while 78 people used pipes less often and 5,237 had quit.

Pipes, hookahs and all other tobacco products are just as harmful as a cigarette. post-gazette.com
Pipes, hookahs and all other tobacco products are just as harmful as a cigarette. post-gazette.com

During the study period, 51,150 people died of all causes.

With a daily cigarette, cigar or pipe habit, people had an elevated risk of death from tobacco-related cancers including malignancies of the bladder, oesophagus, larynx, lung, mouth and throat, and pancreas.

Nondaily users

Even with a nondaily cigarette habit, people were more than six times more likely to die of lung cancer than individuals who never used tobacco. They also had more than seven times the risk of dying from a chronic obstructive pulmonary disease, more than four times the odds of death from oral cancers, and 43 percent higher odds of death from a circulatory system disorder.

Current cigar smokers had more than three times the odds of dying of lung cancer, and for current pipe smokers, the risk was 51 percent higher, compared with never-smokers.

The results were limited, however, by the relatively small numbers of cigar and pipe smokers in the sample, the authors noted.

Cigarettes, hookah, pipes, cigars all are equally harmful.
Cigarettes, hookah, pipes, cigars all are equally harmful.

Another limitation was that survey questions about tobacco use changed over time and didn’t determine how often nondaily smokers might have used cigarettes, cigars or pipes.

Even so, the results suggest that doctors may need to broaden how they discuss smoking with patients to make sure people understand they’re at risk even when they don’t have a daily habit, said Dr. Michael Ong of the University of California-Los Angeles and VA Greater Los Angeles Healthcare System.

Also Read:  Beware! Vapor smoke from E-cigarettes are just as harmful, says a new research

“Patients often do not associate the occasional use of cigar or pipes with health risks, but this study shows that current, particularly daily, cigar use is associated with increased overall risk of death,” Ong, who wasn’t involved in the study, said by email.

Doctors also need to broaden their message about smoking and cigarettes to include other tobacco products that are becoming more popular, said Judith Prochaska, a researcher at Stanford University in California who wasn’t involved in the study.

e-cigarettes
Smoking e-cigarettes are not a healthier alternative to smoking. cigarettes Pixabay

Traditionally, doctors have asked just whether people smoked cigarettes, but they should instead be questioning patients more broadly about tobacco use, Prochaska said by email.

“The tobacco landscape has been changing dramatically,” Prochaska added. “While cigarettes remain the primary tobacco product used, cigars, smokeless tobacco, e-cigarettes, hookah, and even pipe tobacco have seen gains in use, while cigarette use in the U.S. has been declining.” VOA