Fight against cancer gets a power couple
Allison, Sharma push immunotherapy forward
CHICAGO -- Cancer researcher Jim Allison stands at the edge of a small stage, fiddling with his harmonica, his unruly gray hair hanging almost to his shoulders. Soon, surrounded by eight other cancer experts who also happen to be musicians, he'll be growling out the classic "Big Boss Man" before a boisterous crowd at the House of Blues.
It's a fitting number, says Patrick Hwu, who plays keyboards for the band and is Allison's colleague at the University of Texas MD Anderson Cancer Center in Houston. "When it comes to immunotherapy, he is the big boss man."
Few would disagree. In recent years, Allison's work has ignited a revolution in oncology treatment that frees the immune system to attack malignant tumors. Patients near death have returned to live full lives. The drug class he pioneered,
called checkpoint inhibitors, now includes a half-dozen therapies that have spawned a billion-dollar market. So stuffed is his office with scientific awards that some sit in boxes on the floor. He frequently shows up on the shortlist of contenders for the Nobel Prize in medicine, which is being announced Monday.
But amid the successes, these are challenging times for Allison and the oncologist who is his key partner — and who typically is front and center in the audience when his band plays at fundraisers like this. Padmanee Sharma is a formidable researcher and immunologist in her own right at MD Anderson, a specialist in renal, bladder and prostate cancers. She is also Allison's wife.
In their particular corner of the universe, they are the ultimate power couple. Yet they, like other immunotherapy enthusiasts, find themselves grappling with the downsides of the new treatments. The therapies can cause serious side effects and, while effective for some patients, are far from foolproof. And they have largely been a bust for cancers of the prostate and pancreas.
Allison and Sharma feel the frustration acutely, saying that many more people must be helped. "We need to get the numbers much, much higher," he says.
Even as they pursue the next breakthrough, their lives are a frenetic mix of science and celebrity. Allison's role in developing immunotherapy has won him the adulation of both patients and philanthropists. The couple has flown on philanthropist and former financier Michael Milken's private jet, been escorted on backstage tours by U2's the Edge and attended highwattage Vatican stem-cell conferences. At the Smith & Wollensky's where they frequently dine in Houston — where Allison proposed to Sharma — there are wall plaques inscribed with their names near their usual table.
Still, they reserve most of their energy for their science. They say immunotherapy's problem is that its use in patients has outpaced a fundamental understanding of how it works.
To remedy that, they are running an ambitious program that links animal research, novel human trials and intense monitoring of tumors via repeated biopsies. By analyzing the malignancies before, during and after treatment, they hope to better understand the interaction among the cancer, the treatment and the immune system. They know that using combinations of therapies for cancer will probably be the key to better outcomes for patients, but they need to figure out exactly which drugs to use, and how.
Allison doesn't hesitate to tell Sharma what works best for laboratory research. She pushes back on any suggestions that might not help patients, reminding Allison he isn't a physician.
And if they can't compromise, who wins?
"Pam," says the gravelly voiced Allison. "She's louder."
"I just want things to move things faster," she counters.
On the sprawling MD Anderson campus, Sharma speed-walks, doling out medical advice, pep talks and the latest test results.
She warmly greets Michael Lee Lanning, a retired Army lieutenant colonel who was diagnosed with kidney cancer in 2003. Within three years, the disease had spread throughout his body, and doctors sent him home with painkillers and phone numbers for hospice. He was 59.
Looking for a reprieve, he went to MD Anderson and met Sharma. "She looked me in the eye and said, 'Everyone will die, and some will die sooner,' " he recalled. A "cold b----," he told his wife.
But as he ran through treatment after treatment, Lanning came to appreciate Sharma's refusal to give up. Two years ago, she had him enroll in a trial testing a combination of radiation and Yervoy, a medication developed by Allison that was the first checkpoint inhibitor approved by the Food and Drug Administration. The treatment kept Lanning's cancer under control until this past December, when the tumors once more began growing and he repeated the one-two punch of radiation and Yervoy. More recently, to keep the tumors in check, he began taking a different immunotherapy drug.
"I didn't think I'd make it to 60," said Lanning, who is again stable. Now he's 71 years old. His beloved granddaughter, who was 8 when he was diagnosed, is now in college.
Sharma has pushed for close monitoring of tumors in various stages of treatment for years, believing that it provides critical clues about why only some patients respond to immunotherapy and about how to design subsequent trials and experiments. Allison, a fan of the strategy, made its broad expansion a condition of his move from Memorial Sloan Kettering Cancer Center in New York to MD Anderson in 2012. Today, about 100 of the center's trials involve such intense surveillance.
While other cancer hospitals do similar analysis, the scale of the effort at MD Anderson sets it apart. "I'm jealous," said Charles Drake, co-director of the cancer immunotherapy programs at Columbia University Medical Center in New York. "They can apply state-of-the-art analytical tools to tumor specimens before, during and after treatments and see the results in real time."
Now Sharma and Allison are bringing their approach to advanced prostate cancer, which is notoriously resistant to immunotherapy. Previous research has shown that combining two immunotherapy drugs might be better than using just one. In a trial overseen by Sharma, one drug is used to drive T cells, the foot soldiers of the immune system, to the tumor, and a second to block proteins that keep those soldiers from attacking the malignancy.
"We have to try," she says. "At least these treatments give our patients a chance."
By outward appearance, Allison and Sharma are opposites. She's 47, striking and model-thin; he's 69, rumpled and pudgy.
Just as pronounced are their similarities. They bonded years ago over their shared obsession with T cells, and these days, Sharma says, "we talk about data all the time, at dinner, while brushing our teeth."
Allison grew up in a small town in South Texas where his country-doctor father made house calls. His mother died of lymphoma when he was 11 — just the first of many family losses to cancer. Two uncles and a brother later died of the disease. Allison has battled early-stage melanoma, bladder and prostate cancers.
He went into cancer research not because of family history but because he always wanted to be the first person to figure something out. Early on in classes at the University of Texas at Austin, he realized that medical school wasn't for him. "If you are a doctor, you have to do the right thing; otherwise, you could hurt somebody," he says.