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The game changer

Conquest - Summer 2014

A blues-loving scientist from a small town in South Texas shook off the immunotherapy naysayers and made believers out of everyone

By Scott Merville


James Allison, Ph.D., loves to sing the 
blues. The scientist and harmonica 
player formed a blues band with other 
immunotherapy experts called The 
Checkpoints, which has a standing gig at 
the House of Blues in Chicago during the 
annual meeting of the American Society 
of Clinical Oncology each summer.
Photo: Wyatt McSpadden

Back in 1977, James Allison arrived at MD Anderson’s Science Park in Smithville, Texas, with an itch to discover something new. It was the music-loving, harmonica-playing scientist’s first faculty position, and he was happy to be near Austin, his favorite city.

There was no way of knowing then, but Allison’s initial research on the immune system at MD Anderson laid the groundwork for his return in 2012 as the father of immune checkpoint blockade — an entirely new way of treating cancer that’s yielding unprecedented results.

Thanks to his clinical collaborators, he’s been fortunate enough to meet some of those saved by his drug, ipilimumab (Yervoy®), the first ever to improve survival for patients with advanced melanoma. According to American Cancer Society predictions, the disease will kill more than 9,700 people in the U.S. in 2014.

One of the most dramatic stories belongs to an original phase I clinical trial patient in Los Angeles.

“The patient just wanted to live long enough to see her teenage sons graduate from high school,” says Allison, chair of Immunology. “That was 14 years ago. She’s lived to see them go to college, go to graduate school, start their own families and get established in their careers …” His voice trails off and his eyes mist. “I get emotional talking about them. That’s what it’s all about.”

Allison brings immunotherapy expertise to MD Anderson.
Click on the image to watch the video

The basic science behind success

The journey from Allison’s laboratory research at MD Anderson to Food and Drug Administration approval of ipilimumab for metastatic melanoma in 2011 was arduous and often frustrating. It included stops at other prestigious research institutions such as the Cancer Research Laboratory at the University of California, Berkeley, and Memorial Sloan Kettering Cancer Center, the travails of drug development and the quirks of pharmaceutical companies and clinical trials.

“Jim has great scientific intuition and he’s stubborn — or maybe persistent is a better word. He tells you exactly what he thinks,” Patrick Hwu, M.D., says of Allison, who goes by Jim.

“He had the vision to see the research through to a paradigm changing treatment strategy,” adds Hwu, chair of Melanoma Medical Oncology, who’s both a scientific and musical collaborator of Allison. “I truly appreciate what he’s done for my patients.”

Follow-up studies show an unprecedented 22% of late-stage melanoma patients treated in ipilimumab clinical trials survived for at least four years. Meanwhile, checkpoint  blockade is being extended to treat other cancers, and the journal Science named cancer immunotherapy its 2013 Breakthrough of the Year.

Allison lost his mother to lymphoma when he was 11 years old and a brother later on to prostate cancer, a disease he himself has survived.

“My family has suffered greatly from the ravages of cancer, so cancer treatment has always been in the back of my mind,” he says.

“But I didn’t set out to develop a cancer treatment. If I had, I probably would have missed something important because the target we found isn’t on tumors, it’s on T cells,” Allison says. “Checkpoint blockade emerged as a cancer therapy only because we first uncovered the basic science and biology of T cells, the immune system’s primary attack cells. It’s a classic example of how understanding basic science can lead to new disease treatments.”

Allison’s return to MD Anderson in November of 2012 came with a $10 million recruitment grant from the Cancer Prevention and Research Institute of Texas and an MD Anderson commitment of $30 million to develop an immunotherapy program that Allison says is unmatched in its scientific and clinical capabilities.

“One appeal of being a scientist is being the first person on the planet to know something. It’s kind of egotistical, but I think most scientists are driven at least in part by that ambition. There was so little known about T cells, their function was a black box.”

— James Allison, Ph.D.

“Immunotherapy is the most exciting and promising area of cancer research today, and its potential is just beginning to be realized,” says MD Anderson President Ron DePinho, M.D. “We’re proud to have Jim leading our efforts to expand and hone this approach as executive director of MD Anderson’s Moon Shots Program immunotherapy platform.” Allison, who’s encountered a lot of immunotherapy naysayers over the years, acknowledges DePinho’s commitment to advancing the treatment.

“Ron is the first cancer center leader to say ‘we’re really getting into this big,’” he says. “I wouldn’t be here without him.”

First stop: Research Park in Smithville

The T cell ignition switch

CD28: The gas pedal

CTLA-4: The brakes

The slow road to drug approval

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© 2015 The University of Texas MD Anderson Cancer Center