Dr. Phil Greenberg remembers a time, not so long ago, when immunotherapy was relegated to the fringes of cancer research. Now, therapies that harness the powers of the immune system to eradicate cancer splash across magazine covers and generate the biggest buzz at scientific conferences.
Greenberg kicked off a forum on Wednesday at Fred Hutchinson Cancer Research Center that brought together some of his fellow leaders in the immunotherapy arena from across Seattle and around the country to discuss the latest developments in their field.
Alongside the traditional “three pillars” of cancer therapy — radiation, chemotherapy, and surgery — “I think there’s no question that immunotherapy is now a fourth,” Greenberg said.
Now in its fourth year, the sold-out forum was organized by Xconomy, a tech- and business-focused online news outlet with outposts in 11 innovation hubs around the country, including Seattle.
Here are five of the top highlights from the symposium:
When lung cancer specialist Dr. Renato Martins completed his training years ago, he knew by name every single one of his patients who survived two years after treatment. It wasn’t because Martins has an unusually powerful memory: It was because there were so few of them.
Now, he has so many patients who have survived twice that long that he couldn’t possibly rattle off all their names, he said in a talk at the forum. The difference is all the new therapies that have come on board for lung cancer, including checkpoint inhibitors, a class of drug that blocks a braking system cancers use to dampen the immune response.
“This is a completely different landscape,” Martins said.
For certain lung cancer patients, a checkpoint inhibitor is now the preferred first-line therapy, before chemotherapy. Patients with other cancers, such as advanced melanoma, have also seen a transformation in care with the approval of this class of immunotherapy drug, although doctors and researchers are still trying to get a handle on the best treatment regimens and the side effects of these approaches.
Other types of immunotherapies involve administering cancer-fighting immune cells to patients. These are still experimental but have shown very promising results in early clinical trials in blood cancer. The first of these therapies are likely to be approved in patients with advanced disease by the FDA this year.
“We are just at the start of this,” said Dr. Hans Bishop, CEO of Fred Hutch spinoff Juno Therapeutics, which is developing cellular immunotherapies for cancer. “What’s coming is going to be unbelievable.”
Panelist Dr. Michael Kalos, of Eli Lilly and Company, said the first generation of immunotherapy trials were “like spaghetti on a wall” — as in, let’s just throw some stuff at this cancer and see what sticks.
While the relative successes in these trials of certain immunotherapies compared to traditional chemotherapies led to FDA approvals in particular cancers, it is clear that only some patients are helped by these strategies. It is also clear that many cancers can eventually “escape” from a treatment that was once successful in controlling its growth.
The next steps: continue learning about cancer biology and use that knowledge to design better treatments. Throughout the forum, speaker after speaker said it is obvious that combination immunotherapy strategies will be needed to interfere in the numerous and dynamic mechanisms cancers use to avoid immune attack.
“The entire field believes that combinations are the future,” said Dr. Jill O’Donnell-Tormey of the Cancer Research Institute, a New York-based nonprofit that funds research on cancer immunology. “The question is, ‘How are we going to get there?’”
It will take a smart approach, based on a deep understanding of tumor biology, to find the best combination treatments to keep more cancers in check for longer, speakers said. Researchers around the world, including at Fred Hutch, are now teasing apart the intricacies of cancer immunobiology to get at these answers. Biotech startups, like Fred Hutch spinoff Adaptive Therapeutics, whose CEO Chad Robins spoke at the forum, are bringing new tools for understanding the immune system to market to accelerate research.
Combination immunotherapies could include something as simple as giving a patient two different FDA-approved drugs, as in many ongoing trials, or as complex as combining multiple types of genetically engineered, cancer-fighting T cells in one high-tech punch.
That’s the premise of a new trial recently opened at Seattle Children’s Hospital for kids with advanced leukemia, said Dr. Mike Jensen, a pediatric immunotherapy researcher at Children’s and Fred Hutch.
Jensen and collaborators have previously tested a strategy in which patients’ disease-fighting T cells are genetically engineered to equip themselves with a molecule called a chimeric antigen receptor, or CAR, that allows them to target cancer cells.
Their latest strategy is to combine CAR T-cell therapy, as the experimental treatment is known, with an infusion of another group of genetically engineered T cells. But instead of being engineered to target cancer cells, like CAR T cells, these cells are engineered to help keep the CAR T cells active: Specifically, they are programmed to carry, like a red flag, a version of the leukemia target that CAR T cells recognize. The idea is that the presence of these cells will keep the CAR T cells on alert for any leukemia cells that would otherwise be able to hide from the immune system and regroup.
Innovations in the lab to create next-generation designs of engineered T cells are proceeding at a far more rapid pace than is possible to translate into clinical trials, Jensen said. These laboratory breakthroughs, if successfully translated into the clinic, could help CAR T-cell therapy overcome some of the formidable defenses to immune attack found in solid tumors like brain cancer, he said.
Someday, Jensen envisions, a child newly diagnosed with cancer will be able to avoid chemotherapy — and its harmful long-term side effects on young bodies — thanks to this type of emerging approach.
“If we don’t dream about it,” Jensen said, “it certainly won’t happen.”
To get us to this brighter future of cancer care, we will need intensive collaboration between academic researchers, industry and nonprofits. And we’re already on our way, said Eli Lilly’s Kalos.
“It’s absolutely the path in every way in the future development of immunotherapy,” Kalos said. “And the genie’s already out of the bottle.”
O’Donnell-Tormey of the Cancer Research Institute highlighted an effort her organization spearheaded to do this. CRI acts as a go-between for academic investigators, pharmaceutical companies that own immune-modulating drugs, and philanthropists interested in funding research. The system the organization set up frees companies to provide their compounds for research in a way that does not endanger their intellectual property. And it allows independent researchers to gather critical information about the potential of these drugs for cancer treatment that the companies can then build on to potentially advance the drugs to market.
This kind of approach is especially important given the role that combination immunotherapies will play in the future of cancer care, Kalos said. Many of the best combinations will undoubtedly involve therapies owned by different companies. Bringing the different players together to build trusting relationships is key and requires finding a common language and common objectives.
The CRI’s approach “is a model for other nonprofits” that want to help advance medical research, Kalos said.
The skyrocketing costs of medical care has burst into the public consciousness in recent years, with the emergence of more and more extremely expensive new therapies — among these, checkpoint inhibitors for cancer.
The costs and value of immunotherapy were on everyone’s mind at Wednesday’s forum as well. The conversation covered costs to society and patients, insurance coverage and the impact of these therapies on the already-strained capacity of our healthcare system.
Researchers have estimated that treating a single patient for a year with a checkpoint inhibitor can cost hundreds of thousands of dollars, of which tens of thousands would be the responsibility of the patient, even with good insurance coverage.
But what if a single infusion of cancer-fighting T cells could eliminate a patient’s cancer for good? The upfront cost may be large, but “trivial” in comparison to long-term immunotherapy drug treatment, said Dr. Sylvia Lee of Fred Hutch, who studies a type of experimental T-cell therapy known as tumor-infiltrating lymphocyte therapy, or TIL therapy.
And the question of cost is different than that of value, which measures not just what you pay, but what you get for what you spend. A therapy that gives someone many years of healthy, productive life is more valuable than a therapy that costs the same but doesn’t keep the cancer at bay for long, or that causes significant disability.
Our society may need to come up with different payment models to accommodate a highly front-loaded cost structure, said Juno CEO Bishop.
The question is “how much money the system saves if you have a therapy that’s curative,” even if the initial cost is high, Bishop said.
Lee, the T-cell therapy researcher, leads one of only five academic research programs in the country working on TIL therapy, in which a diverse collection of patients’ own cancer-fighting immune cells are isolated, multiplied and reinfused to treat their cancers. And through this work, Lee has seen the value of curative immunotherapy approaches to individual patients firsthand.
Once an avid hiker, a patient of hers could no longer go on the long treks he enjoyed after his metastatic melanoma formed a painful mass on his leg. The cancer had come back even after treatment with a checkpoint inhibitor. But he enrolled in a clinical trial she led of TIL therapy for this disease, and he is now more than two years out, cancer-free, and back to hiking. He will soon be embarking on his second African safari since enrolling on that trial.
Lee’s goal, and the goal of every researcher developing cancer immunotherapies, is to have every story turn out like this.
“This is what we hope to be able to do for more patients,” Lee said.
Susan Keown was a staff editor and writer at Fred Hutchinson Cancer Center from 2014-2022 who has written about health and research topics for a variety of research institutions. Find her on Twitter @sejkeown.