Source: Boston Globe
Author: Karen Weintraub

Long envisioned drugs to harness the immune system could reshape treatments

 

For more than a century, doctors and patients have dreamed of using the body’s own defenses to fight cancer. Why, they wondered, can’t the immune system – so good at tracking down and destroying intruders – attack the tumor cells that invade healthy tissue?

Finally, science is catching up with this vision.

Just reaching the market in a big way, so-called therapeutic vaccines turn a patient’s immune system against the cancer and help prevent a recurrence. If the early promise of these vaccines is realized, they will soon join the basic arsenal for fighting all cancers, several researchers said.

“We really are in a transformative moment,’’ said Dr. Glenn Dranoff, professor of medicine at Harvard Medical School and a medical oncologist and immunologist at the Dana-Farber Cancer Institute.

Prostate cancer patients were the first to benefit. A therapeutic vaccine called Provenge received federal approval last year after studies showed it safely extended the lives of advanced prostate cancer patients for an average of 4.1 months.

Then came a vaccine called Yervoy, designed to attack melanoma, a particularly dangerous form of skin cancer.

Cancer generally turns down the body’s immune response to a tumor; Yervoy is designed to turn it back on, enhancing the immune system’s ability to kill cancer cells.

Many more cancer vaccines are under development, with hundreds of trials underway in patients with breast, prostate, lung, kidney, colon, cervical, brain, and pancreatic cancers, as well as lymphomas. Once companies confirm the effectiveness of these therapies in one type of cancer, they are likely to try them in others.

“From the immune point of view, the distinction between one cancer type and the next is not so important,’’ said Dranoff, who did early work on Yervoy. “That’s part of why so many companies now are developing these agents.’’

The market responded enthusiastically when Provenge, made by Dendreon Corp. of Seattle, was first approved in April 2010, and that drove excitement around other potential vaccines.

The fervor has since cooled, as sales fell well below expectations. But the drug’s $200 million or so in revenue still puts its first-year sales among the top five or six ever for a cancer product, according to the company president and chief executive, Dr. Mitchell H. Gold.

The vaccines have substantial price tags: Provenge is on the market for $93,000 for three treatments and Yervoy is $120,000 for four treatments.

Developers insist those costs are in line with chemotherapy’s costs and worthwhile because they block cancer from spreading or recurring, at least for a while.

“The really expensive part of cancer treatment is treating the recurrence,’’ said Estuardo Aguilar-Cordova, chief executive of Advantagene Inc., of Auburndale, which is developing a prostate cancer vaccine, ProstAtak.

Radiation or surgery after initial diagnosis costs about $50,000, he said; treating cancer that recurs can easily cost $500,000.

“It’s a lot less expensive for our society as a whole to prevent the disease than to treat the disease,’’ he said. “That’s part of the promise’’ of cancer vaccines.

In an early trial designed to look at safety, ProstAtak cut the prostate cancer recurrence rate from 30 percent to 10 percent, Aguilar-Cordova said. His company has just begun a larger trial at hospitals nationwide, including at UMass Memorial Medical Center in Worcester. The trial should help determine how many patients remain recurrence-free, and for how long.

Cancer vaccines are designed to supplement – not replace – existing treatments. And multiple vaccines may work better coupled with those treatments than alone, several scientists said.

Researchers say the vaccines are at a starting point and expect they will improve substantially over time.

“This is really the first wave and proof-of-principle kind of stuff,’’ said Dr. Philip Kantoff, chief clinical research officer at Dana-Farber and a professor at Harvard Medical School.

Kantoff led early trials for Provenge and said he was surprised when the therapy worked.

More potent vaccines that extend life spans even longer than the current ones are certainly coming, said Darrell J. Irvine, an associate professor at MIT’s David H. Koch Institute for Integrative Cancer Research.

Of course, there are still many unanswered questions about how the immune system works, Irvine said, and so those greater potencies may also pose greater risks.

“Before, our cancer vaccines were so weak, there wasn’t much concern’’ that they could trigger a systemic immune reaction, like the autoimmune diseases psoriasis, multiple sclerosis, or rheumatoid arthritis, he said.

“Now, perhaps we’re reaching the stage where the threat of autoimmunity will be something to worry about.’’

William Bradley Coley, a 19th-century surgeon, was the first to try immunotherapy on a patient, giving a strep infection to a man with throat cancer in 1891. It helped the man live another eight years.

Though Coley repeated the experiment with 100 more patients, his approach was criticized and was quickly eclipsed by radiation therapy.

In the 1980s and early 1990s, the field of immunotherapy began attracting researchers like Dranoff, Gold, Aguilar-Cordova, and Kantoff, and finally, their work is paying off.

“There’s really been just a constellation of advances from many aspects of immunology and clinical research and understanding that have led to this moment,’’ Dranoff said.