Inaugural 'Oncology Summit' addresses academic-industry partnerships

Variations on the immunotherapy theme

The majority of Friday’s scientific talks focused on the latest updates from the immunotherapy world. Merck scientist Dr. Rene de Waal Malefyt described drugs known as checkpoint inhibitors, which include Merck’s Keytruda, or pembrolizumab, and work by releasing the brakes on the body’s natural immune system, allowing it to better recognize and attack cancers. 

But even when such drugs work, they don't work for all patients, so the next step in the immunotherapy field is to figure out what researchers can add to checkpoint inhibitors to boost their power, said Fred Hutch immunotherapy researcher Dr. Mac Cheever, who directs the multi-center Cancer Immunotherapy Trials Network or CITN, headquartered at the Hutch. And that’s the tricky part.

“The scientific or academic goal is to understand why (some) patients don’t achieve a complete response and why (some) patients don’t respond (to checkpoint inhibitors), so there’s a lot of work to do there," Cheever said. "There are a number, not quite an infinite, but an uncountable number of agents that can be used in this situation."

In his opinion, biotech companies haven’t approached such combination therapies in a very logical way, Cheever said. Many industry researchers simply tested the inhibitor checkpoints in combination with other drugs their own company produces, or those their partners produce, rather than picking combinations with a scientific rationale. CITN researchers are aiming to approach these combinations more systematically, Cheever said, by prioritizing drugs that act in a certain way on the immune system.

Research presenters at the summit also touched on other forms of immunotherapy in addition to checkpoint inhibitors, including:

• Tumor-infiltrating lymphocytes, a type of immunotherapy that extracts a tumor’s dormant immune cells and reawakens them in the laboratory to better recognize and attack cancer cells. Fred Hutch’s Dr. McGarry Houghton is currently leading preclinical studies of this approach for non-small cell lung cancer, with the goal of starting a clinical trial at the Hutch.
• Fred Hutch bioengineer Dr. Matthias Stephan presented updates from his team’s work developing an “off-the-shelf” version of CAR T-cell therapy, in which nanoparticles bearing DNA instructions to reprogram a patient’s T cells to recognize and kill cancer cells would be injected directly into the patient’s bloodstream.
• Dr. Mitch Gold, former CEO of the now defunct Seattle biotech company Dendreon, introduced his relatively new startup, Alpine Immune Sciences, which seeks to understand and target the “immune synapse” — the junction between two different types of immune cells that involves a myriad of different molecular interactions — with the goal of modulating the immune system for cancer and other diseases.

Beyond immunotherapy — from umbilical cords to scorpion venom

The Seattle life sciences scene isn’t all immunotherapy though, as several of the presenters reminded their audience. Fred Hutch cord blood transplantation researcher Dr. Colleen Delaney enthusiastically described her newest venture, Hutch spin-off Nohla Therapeutics, for which Delaney serves as chief medical officer. She and her colleagues have shown the power of stem cells taken from umbilical cord blood to save lives when used as a replacement for a traditional transplant, but because each cord contains only a small number of such cells, patients who receive this source of stem cells are subject to infections and other complications until those cells can multiply and repopulate their damaged immune systems.

Nohla’s goal, Delaney said, is to commercialize a product she developed at the Hutch using laboratory techniques to expand cord blood stem cells in the laboratory, creating an off-the-shelf stem cell product that can protect patients during that vulnerable period. Early-stage tests using the expanded cells either for transplant patients or leukemia patients whose white blood cells are damaged by intensive chemotherapy have shown promise and the product is currently being tested in a randomized Phase 2b clinical trial, Delaney said.

Heather Franklin, CEO of Hutch spin-off Blaze Bioscience, described their progress with Tumor Paint products for breast cancer and pediatric brain cancer. Developed by Fred Hutch pediatric brain cancer researcher Dr. Jim Olson, tumor paint uses a small protein derived from scorpion venom attached to a fluorescent molecule to “light up” brain tumors — showing brain surgeons where to cut to remove all the tumor. Half the time, such surgeries for children with brain cancer miss residual parts of the tumor, Franklin said, so a product like this is sorely needed.

The Blaze tumor paint product, BLZ-100, is currently being tested in Phase 1 clinical trials for pediatric and adult brain cancer. The researchers are also testing the drug for patients with breast cancer who are undergoing surgery, to improve the chances that the surgeons can get the tumor out with clean margins, Franklin said. A quarter of women undergoing lumpectomies for breast cancer need repeat surgery because some of the tumor was missed, she said.

Merck’s head of North American Innovation Hubs, Ben Thorner, wrapped up the day’s talks and conversations.

“As I think about all the different things I learned about today, the work that’s being done here at the Hutch, the work that’s being done in small companies and large companies like Merck, how much of it is happening as a result of genuine collaboration,” Thorner said. “That is exactly why we put this day together.”