Robert Hood / Fred Hutch
Cancer immunotherapy, buoyed by promising clinical data and a resurgence in research investment, is riding an optimistic wave and has many in the field redefining their expectations of success for new treatments from incremental advances in patient response to complete regression of tumors.
Experts from academia, established biotech players and youthful startups came together this week at Fred Hutchinson Cancer Research Center to speak about the latest developments and the challenges ahead at “What’s Hot in Cancer Immunotherapy,” an Xconomy Forum.
The recent explosion in the field was underscored by the forum’s closing session, a Q&A with two members of the leadership team at Juno Therapeutics, the Seattle-based startup that announced Thursday it had closed its Series A round of venture funding with a jaw-dropping $176 million.
Fred Hutch’s Dr. Stanley Riddell, the event’s keynote speaker and Juno Therapeutics scientific co-founder, compared the improvements in patient survival that cancer immunotherapy researchers are seeing to those last seen decades ago, when bone marrow transplantation shifted the landscape of blood cancer treatment forever.
Dr. Larry Corey, president and director of Fred Hutch, also highlighted this link in his opening remarks. The Hutch’s role in pioneering transplantation as a cure for certain blood cancers, he noted, made the organization a fitting venue for Xconomy’s event. The discovery that bone marrow transplantation’s power lies in the ability of the donated immune system to eliminate the recipient’s cancer provided one of the first examples of a successful immunotherapy. “We have been working on the essence of that for over 25 years,” Corey said.
One reason for the crescendoing buzz around cancer immunotherapy is that, unlike bone marrow transplantation, these treatments have the potential to tackle a wide variety of tumor types. The forum’s eight presenters discussed approaches that are already being tested in more than a dozen cancer types, and researchers are only beginning to “touch the surface” of the possible strategies that immune-based treatments make possible, said Riddell.
Unleash the killer cells
The immune system is a powerful deterrent against cancer growth — at least until tumors adopt strategies to escape detection or keep immune attack in check. Several therapies designed to help remove these roadblocks and unleash the immune system have passed or are nearing the finish line of FDA approval. Other therapies are aimed at giving immune cells a push in the right direction.
Speakers at the event shared highlights of some of the products now in development, including small-molecule drugs, antibody- and cell-based therapies, and engineered nanoparticles. The common thread that emerged across the presentations (see below for a complete list) was a sense of excitement, both about the progress to date and the possibility of bigger and better results in the future. “We’re in a renaissance of cancer immunotherapy,” said Deborah Law, vice president of biologics discovery at Merck.
Emcee Luke Timmerman, who has been covering biotech news for years, said he began to notice the momentum building around cancer immunotherapy nearly a decade ago. But within the last year especially, he said, the field had gone from “exciting” to “really, really exciting.”
Bringing the immune system to heel
As impressive as responses to many of these experimental therapies can be, however, there are still many questions to address and barriers to overcome.
Researchers are still in early stages of understanding how best to deploy these treatments, including in combination with conventional therapies as well as other immune-based approaches. It’s also unclear how to predict which patients will respond, how best to measure these responses, or even how to know which tumors are the best candidates for each therapy.
As researchers delve into such questions, they are also learning some surprising but encouraging lessons. For example, immunotherapy may be an option for tumor types or patients previously thought to be poor candidates. Therapies designed to release the brakes that cancer puts on the immune system showed dramatic results in patients with non-small cell lung cancer, though researchers “had no clue it would be immune-responsive,” explained Riddell. And Ira Mellman, vice president of cancer immunology at Genentech, observed that immunotherapy has produced encouraging results even in patients whose immune systems were thought to have been ravaged by the chemotherapy they’d previously received.
Going forward in a big way
In a lively closing chat moderated by Timmerman, Juno Therapeutics’ Hans Bishop and Robert Nelsen discussed small molecules, dramatic results, cell therapies, and the long-view approach they’re taking to building a biotech company and developing effective cancer immunotherapies.
Bishop noted the dire need for better cancer therapies. “The standard of care in most of these tumors is still abysmal,” he explained — but cancer immunotherapy promises to turn this situation around. Bishop and Nelsen’s enthusiasm doesn’t merely rest on the dramatic results seen in patients with tumors that had long since ceased responding to conventional therapies, but on the untapped potential and high quality of the science that Nelsen said is “still on the drawing board.”
This is why Juno is dedicated to a long-term vision, the men explained. The company is funneling a tremendous amount of resources into research and development, including taking a step back to gain deeper insights into tumor biology as well as exploring the best ways to systematize the production and distribution of immunotherapies.
As Nelsen explained, Juno is “putting on the afterburners” to move many different projects forward in parallel in the coming year.
Robert Hood / Fred Hutch
Shape of immunotherapy to come
The future of immunotherapy will be dramatic, explained Mitch Gold, previously the CEO at Dendreon, now executive chairman of Alpine Biosciences. He stressed the necessity of working toward more effective, less toxic, and easier-to-administer therapies — and noted that the path to achieving this dream is as yet undefined.
Gold compared the state of cancer immunotherapy research to the start of a football game: “We’re still in the first quarter of what’s possible.” How challenges are addressed will help shape the field’s trajectory, and “the companies here in the room are the ones that are going to define that,” he said. The science happening now, he concluded, is “more exciting than anything else going on in the world.”
Sabrina Richards is a staff writer at Fred Hutchinson Cancer Research Center. She has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a Ph.D. in immunology from the University of Washington, an M.A. in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at firstname.lastname@example.org.
Andrea Detter is the deputy editor at Fred Hutchinson Cancer Research Center. Reach her at email@example.com.
Following opening remarks by Jim Edwards and Luke Timmerman, representing Xconomy, and Fred Hutch’s Dr. Larry Corey, eight leaders in the field addressed a packed auditorium as part of the “What’s Hot in Cancer Immunotherapy” forum:
- Deborah Law, vice president of biologics discovery at Merck, described her company’s antibody that targets an inhibitory molecule known as PD-1. In one study, the therapy reduced tumor size in 74 percent of patients with advanced melanoma.
- Ira Mellman, vice president of cancer immunology at Genentech, presented data on an antibody that instead targets PD-1’s binding partner PD-L1. In clinical trials, more than 20 percent of patients with resistant cancers responded to anti-PD-L1 treatment.
- Teresa Foy, chief science officer at recent Seattle start-up Oncofactor, presented progress on an antibody they are developing to target another molecule involved in regulating the immune system, dubbed ONCO1.
- Rob Hershberg, CEO of VentiRx, described VTX-2337, which stimulates immune cells to go after tumors.
- Martin Oft, vice president of clinical and regulatory affairs at ARMO BioSciences, presented PEG-IL-10, a specially engineered cytokine that persists in the body and helps shepherd the immune system toward an optimal anti-cancer attack.
- Stanley Riddell, Fred Hutch researcher and Juno Therapeutics co-founder, described his team’s work on CAR T cells, killer immune cells engineered to seek out and attack cancer. The strategy has shown dramatic effects in clinical trials, “melting” tumors in some patients with advanced lymphomas.
- Mitch Gold, executive chairman of Alpine BioSciences, presented a new tactic: a synthetic “protocell” designed to carry large molecule therapies to tumor cells.
- Chad Robins, CEO of Adaptive Biotechnologies, discussed how QuanTILfy — a method that leverages research by Fred Hutch scientists Drs. Harlan Robins and Chris Carlson — can give a window into the number and type of immune cells inside a patient’s tumors and potentially help researchers predict which patients will respond to immunotherapy.