NEW YORK CITY -- Seeing one's research turn into something that benefits people is a dream of every basic scientist, said James Allison, PhD, of the MD Anderson Cancer Center in Houston.
"I'm just lucky enough to have it work for me," he said, speaking at the 4th annual , just hours after he'd been awarded the 2018 Nobel Prize in Medicine for his role in discovering cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
He shared the prize with Tasuku Honjo, MD, PhD, of Kyoto University in Japan, whose research focused on the programmed death 1 (PD-1) protein. Collectively, their work led to treatments such as the CTLA-4-targeting ipilimumab (Yervoy), and nivolumab (Opdivo) and pembrolizumab (Keytruda) that target the PD-1 pathway.
"I think it's really appropriate that this comes during this meeting," said Allison, noting that friends and colleagues of the past 20 to 30 years arrived at his hotel room at 6 a.m. on Monday morning with bottles of champagne to celebrate the prize.
James Allison, PhD, at the Cancer Immunotherapy Conference
"I think the work he did, identifying the [T-cell receptor] had an enormous impact, and he did that virtually solo in a small lab in Texas," said one of those friends, Phil Greenberg, MD, of Fred Hutchinson Cancer Research Center in Seattle.
Allison's work on CTLA-4 inhibition led to development of the first immune checkpoint inhibitor drug, ipilimumab, approved by the FDA in 2011 for advanced melanoma.
Allison cited the team effort of colleagues, from Berkeley to New York City as well as at MD Anderson, as being critical to the work. "The only thing I did with my hands was the first work on T cell receptors, and after that it's been somebody else's work," he said, adding that that's "what it takes to get things done."
"This is a big day," said Jill O'Donnell-Tormey, PhD, chief executive officer of Cancer Research Institute (CRI), one of the organizations sponsoring the conference. "Having been at CRI for 31 years, I never thought I would see this day that the Nobel Prize would be about cancer immunotherapy."
"You have to remember that when Jim discovered CTLA-4 ... nobody thought that immunotherapy was going to become the fourth pillar of how you treat cancer," she said. "Pharmaceutical companies were not interested in touching immunotherapy."
O'Donnell-Tormey cited Allison's persistence as instrumental in getting attention to CTLA-4 inhibition for cancer care, and for showing that a basic discovery can be taken into the clinic and benefit patients.
Greenberg agreed. "It was his ability to not just do the basic science, but to recognize the potential impact and what these things mean, which is one of the things that make him so unique," he said.
"I want to just emphasize that the impact of this award today cannot be understated," said conference co-chair Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai in New York City. "This is a dramatic recognition of Jim's work for the past several years."
Bhardwaj noted that the effects of Allison's discovery will be seen for decades to come, as it has laid the foundation for many new agents, emboldening people in industry, government, and other sectors to invest in science.
"It's a thrill," she said.
Designing Better Immunotherapy Trials
But Allison cautioned that current clinical trials with checkpoint inhibitors and other agents could be better designed.
"There's somewhere in the order of 2,000 clinical trials going on now with checkpoint agents in combination with something else, and that something else is usually just because a company owns it," he said. "In very few cases has there ever been a combination that's based on data, that's based on understanding what happens when the drug confronts the cancer and the immune system."
"There's just not enough patients to mess around like that," he said.
He said that tissue samples are needed so that responding and non-responding patients can be evaluated.
"We know a lot now about what a good signature of response looks like, but you could understand a lot about a combination by knowing what didn't happen," he said.
'Sustained Funding' for Science Is Critical
"In many ways, Jim's story is the best that science has to offer," said Crystal Mackall, MD, conference scientific planning committee member; of Stanford University in California. "When you feed people like this who have the talent and you have the opportunity, this is the kind of thing that can happen."
Allison noted that in writing grant proposals today, too much emphasis is placed on having researchers justify the relevance their work might have on cancer. "How do you know what's going to be relevant or not?" he said. "Nobody who was ever trying to use the immune system to treat cancer would ever have found CTLA-4; there would be no reason to look for it."
O'Donnell-Tormey agreed. "You just have to support really good people and give them the freedom to explore things that they want to explore -- that may go nowhere -- and I think you can learn as much from failure as you do from success."
"We need to have sustained funding in this country," she added, "because I think you can see where science can lead."