Beware the hype: Being realistic about immunotherapy

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immunotherapywebThere’s been a lot of excitement about immunotherapy as a tool to treat cancer. But as leading experts gathered at the Second International Cancer Immunotherapy Conference held recently in New York, several struck an unexpected note of caution, reports Stat News.

“Be critical,” said Dr Philip Greenberg of the University of Washington, who’s also scientific co-founder 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 tumours 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 tumours.

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

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

Harsh side effects from immunotherapy treatments also remain a challenge.

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 tumours from growing the blood supplies they need to survive, in a technique called anti-angiogenesis. But the tumours 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, tumours figure out a new way to grow.

The report says 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.”

The report says cancer biologists pursuing ways to engineer the immune system to attack tumours are acutely aware that tumour cells react to therapies in very complicated ways that, often, thwart the best ideas. But, the report says, 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 commercialised.

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 non-profit sponsors of the meeting.

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

Stat News report

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