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In cancer fight, Novartis focuses on immunity

New project dwarfs similar efforts

Mark C. Fishman (right) and Glenn Dranoff (left) are leading the Novartis cancer immunotherapy push.Suzanne Kreiter/Globe Staff

CAMBRIDGE — Novartis AG, one of the world’s leading cancer drug companies, is making a big bet on emerging science that uses the body’s immune system to fight off tumors.

Novartis already has 22 oncology drugs on the market to treat everything from breast cancer to leukemia, and 25 more under development, a virtual war chest of targeted treatments. Now the Swiss company, which runs its global drug-discovery efforts from the Novartis Institutes for Biomedical Research here, has launched a research group specializing in the field of immuno-oncology.

Last month, Novartis hired a nationally known cancer vaccine authority, Dr. Glenn Dranoff, to lead the group, focusing on three distinct therapeutic areas but also exploring how to combine them with existing cancer drugs.


Dranoff, 55, a former Harvard Medical School professor who long ran the medical oncology program at Boston’s Dana-Farber Cancer Institute, will be based here at the former Necco candy factory that serves as Novartis research headquarters. But he will head a team of about 50 company researchers stretching from Basel, Swizerland, to La Jolla, Calif.

“This is a huge field that’s just beginning,” said Mark C. Fishman, president of the Novartis Institutes and the company’s global research chief, noting that each approach to fighting cancer is currently proving effective for only a limited number of patients.

“We’re trying to educate the immune system to recognize cancer cells as foreign. Our goal is to cure cancer.”

Excitement about immuno therapies has been building over the past 2½ years, since scientists at the University of Pennsylvania reprogrammed the immune system to attack cancer cells in about a dozen leukemia patients, causing complete remissions in some.

A drug developed jointly by Novartis and UPenn showed promising results in an early safety study on patients with solid tumors, according to results presented last weekend at a meeting of the American Association for Cancer Research.


Other big drug makers have also jumped into the race to develop cancer immune therapies — notably Merck & Co., Bristol-Myers Squibb Co., and the Genentech division of another Swiss pharma, Roche AG.

Here in Massachusetts, several smaller companies have cancer treatments on the market, including Takeda Oncology and Ariad Pharmaceuticals Inc., while research start-ups such as Merrimack Pharmaceuticals Inc. and Agios Pharmaceuticals Inc. are active in the field.

But few companies anywhere are working in immune therapies as aggressively and from as many angles as Novartis, according to independent cancer researchers.

“Nobody else in the field has that kind of footprint,” said Dr. Keith Flaherty, a melanoma specialist at the Massachusetts General Hospital Cancer Center. “Novartis is looking at ways to beat up the tumors with targeted therapies while stimulating the immune cells, as well. This is a monumental effort on their part.”

The science is still in its early stages — with patients showing durable responses to experimental drugs targeting tumors affecting 10 to 15 percent of cancer cases. But Flaherty said Novartis and others hope to expand the reach of immune therapies across all cancer types and for a much higher percentage of patients in the next five to seven years.

The company is already a leader in targeted therapies, drugs that attack specific tumors based on their genetic mutations, an effort led by Dr. William Sellers, the Cambridge-based global head of oncology research. Now, with the addition of Dranoff, who will work closely with Sellers, Novartis plans to devote as much as a third of its cancer research to revving up and reorienting the immune system, the body’s natural defense against infectious agents.


One of the first moves of Dranoff’s new immuno-oncology group was to strike a partnership last month with Aduro Biotech Inc., a Berkeley, Calif., immunotherapy company with three drug candidates in clinical trials. Aduro’s experimental drugs target a cell signaling “pathway” — a series of actions among molecules in a cell — known as STING, or stimulator of interferon genes. They aim to induce immune responses, activating cells that fight a variety of cancers.

The Novartis group is also working with the cancer research lab of UPenn professor Carl June on a technology called T-cell modulation. Under the alliance, researchers have been drawing T cells — white blood cells active in immune response — from patients’ blood. Then they alter the T cells, based on the proteins in patient tumor cells, and implant them back into the bloodstream. The modified T cells are able to recognize the cancer cells and then kill them.

A third focus for Dranoff’s group will be so-called checkpoint inhibitors. These drugs work to suppress natural “switches” that act like brakes on molecules regulating the immune system. The switches prevent the immune system from attacking the body’s healthy cells but also its tumor cells. Novartis scientists are seeking to disable “stop signals” and enable “go signals” in three checkpoint-regulating pathways key to sparking an immune response.


Novartis researchers acknowledge that each immuno-oncology approach is so far proving effective for some patients but not others in clinical trials. But by improving their understanding of tumors and the immune system, they hope to find the right combinations that can turn cancers into a chronic disease in the short term and eventually destroy them.

“We want to have a robust tool kit,” Dranoff said. “A finite number of checkpoints are likely to be important for a variety of cancers. We want to be in a position to push this field, take advantage of important opportunities, and create a comprehensive approach.”

Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society in Atlanta, said interest in priming the immune system against tumors dates back several decades. But only in recent years, with improved understanding of genetics and molecular biology, has the science progressed to the point where scientists can develop immune therapies, he said.

“In the 1970s, we said if we can harness the immune system. we could get the body working to fight its own cancer,” Lichtenfeld said. “But we were never able to capitalize on that.

“Now that we’re starting to see some results from new drugs — it’s a very exciting time.”

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Robert Weisman can be reached
at robert.weisman@globe.com. Follow him on Twitter @GlobeRobW.


Correction: An earlier version of this story misstated the name of the American Association for Cancer Research.