Beware the hype: Top scientists cautious about fighting cancer with immunotherapy

NEW YORK — There’s been a lot of excitement about immunotherapy as a tool to treat cancer. But as leading experts gathered here on Sunday, several struck an unexpected note of caution.

“Be critical,” said Dr. Philip Greenberg of the University of Washington, who’s also scientific cofounder of Juno Therapeutics, one of the companies leading the search for immune-based treatments for cancer. “Don’t believe everything you hear.”

Although progress toward harnessing the immune system to attack tumors has been “enormous,” he said, his lab and many others are seeing in more and more studies — in lab mice as well as patients — that “immuno-oncology” will not be as simple as stimulating T cells to attack tumors.

For instance, “we’re seeing relapses despite the fact” that T cells have swarmed a tumor and taken aim at molecules on the malignant cells, said Greenberg, who is also the head of immunology at the Fred Hutchinson Cancer Research Center. And in an early-stage clinical trial for acute myeloid leukemia, there was no improvement in survival even when patients’ immune systems seemed to be attacking their malignant blood cells.

In some cases, the tumors morph so that the target the T cells have been homing in on vanishes. And when T cells do destroy tumor cells, those cancerous cells release potassium — which in turn destroys T cells and keeps them from going after additional tumor cells. Tumors can also send out “inhibitory signals” that shut down T cells, he said.

Harsh side effects from immunotherapy treatments also remain a challenge.

Greenberg spoke at the Second International Cancer Immunotherapy Conference here in New York City.

The difficulties facing immunotherapy mirror hitches in previous “revolutionary” approaches to fighting cancer.

Cancer biologists figured out how to use drugs like Avastin to block tumors from growing the blood supplies they need to survive, in a technique called anti-angiogenesis. But the tumors then figured out another way to grow blood supplies, with the result that many patients relapse and die, having gained little if any additional weeks of life.

In another much-touted technique, drugs knock out the molecules that drive the growth and proliferation of malignant cells. It’s called molecular-targeted therapy and it works as advertised: The drugs do disable the molecules that drive growth — but, again, tumors figure out a new way to grow.

There have, of course, been some breakthrough successes, such as the drugs Keytruda (which helped send Jimmy Carter’s advanced melanoma into remission), along with Opdivo and Yervoy.

Still, the frustrations in creating a consistently effective immunotherapy led one leading cancer researcher to refer this month to the “precision oncology illusion.”

Cancer biologists pursuing ways to engineer the immune system to attack tumors are acutely aware that tumor cells react to therapies in very complicated ways that, often, thwart the best ideas. But of the 1,460 (and counting) scientists from academia, government, and industry at the New York meeting, more than 700 are from industry — an indication of how quickly fairly recent breakthroughs in academic labs are being commercialized.

It’s also indicative of the optimism that despite these setbacks, immunotherapy will eventually be made to work for many cancers and many patients.

“We’ve brought together some of the greatest minds in the field,” said Dr. Margaret Foti, CEO of the American Association for Cancer Research, one of four nonprofit sponsors of the meeting.

By being realistic about how immunotherapy can fail, researchers say, they can make it work for more and more patients.

Greenberg quoted Matt Damon’s stranded astronaut from the film “The Martian” in explaining how his team expected to overcome the obstacles: “We’re going to science the shit out of it.”