Source: The Wall Street Journal

Scientists are scrambling to develop medications that fight cancer by spurring the body’s immune system, a form of treatment that some cancer specialists believe may hold the key to keeping a patient permanently disease-free.

The new efforts come in the wake of recent Food and Drug Administration approvals of Dendreon Corp.’s Provenge, an immunotherapy drug used to treat prostate cancer, and Bristol-Myers Squibb Co.’s Yervoy, for melanoma.

Other immunotherapy drugs are being developed for a number of other cancers, including lung, brain and kidney cancers. Unlike most traditional therapies that attack a cancer directly, immunotherapy uses the body’s own internal defenses to ward off the disease, with the ultimate hope of building up a long-term resistance to the cancer.

“If we are ever going to use the word ‘cure’, the immune system is going to have to come into play,” says Stephen Hodi, director of the melanoma center at Dana-Farber Cancer Institute in Boston.

One of the ways that cancer survives and ultimately spreads through the body is by exploiting a function in all cells that prevents the immune system from killing them. Researchers have found that cancer cells have multiple methods of avoiding detection and suppressing the immune system’s response.

“Why would cancer devote so much energy to avoid the immune system if the immune system didn’t have the potential to reject the cancer?” says Robert Vonderheide from the Abramson Cancer Center of the University of Pennsylvania.

There are big hurdles to advancing the field of immunotherapy. Some of the drugs have significant side effects. And the complex treatments are among the priciest in health care. Yervoy costs about $120,000 for a course of treatment and Provenge $93,000.

The growing interest in immunotherapy comes even as traditional cancer-targeting drugs have become more effective. Still, such drugs often just delay the ultimate recurrence of the disease as tumors develop resistance to the treatment, or some cancer cells survive the therapy and regrow. The hope is that the immune system’s long-term activity against the cancer could stop this cycle.

Varied Approaches
Immunotherapies can work in several ways. They can help the immune system increase its response so that it fights the cancer better; they can stop cancers from slowing down or halting the immune system’s activation; or they can help the immune system find the tumor and kill it.

Provenge, which received FDA approval last year, is made by combining some of the patient’s own immune cells with a specific protein that is created by most prostate cancers. Although the exact mechanism isn’t fully understood, the drug, when given intravenously to the patient, is believed to activate other immune cells to see the cancer as a threat and attack it.

Yervoy is an antibody that binds to a molecule on certain immune-system cells that block them from becoming active. The addition of Yervoy allows the immune cells to become active and fight the cancer.

FDA approvals for Provenge and Yervoy helped set the stage for the current bout of drug research. “We don’t have to convince people this is a good idea,” says Ira Mellman, vice president of research oncology at Roche Holding AG’s Genentech unit, which says it is developing immunotherapy drugs that target advanced solid tumors.

Bristol-Myers Squibb, maker of Yervoy, is investigating the drug’s possible use for other cancers, including prostate and lung. And Dendreon is developing a drug for bladder cancer that works similarly to Provenge.

Other companies are also working on immunotherapy drugs. Roche Holding AG says its research is targeting advanced solid tumors, while GlaxoSmithKline PLC is focusing on several cancers, including lung and melanoma.

Among smaller pharmaceutical companies, Oncothyreon Inc. is working with Merck KGaA on a lung-cancer treatment, and Agenus Inc. is developing therapies in areas including brain cancer and kidney cancer.

There are currently 23 cancer immunotherapies in pipeline development, according to market-research firm Decision Resources.

The FDA currently limits Provenge and Yervoy to patients with advanced forms of their disease and with few other treatment options. Clinical trials have shown that Provenge has minimal side effects, but Yervoy can trigger fatal allergic reactions in some patients.

Side effects will continue to be heavily scrutinized as the drugs are expected to be used earlier in the disease progression or to prevent relapse.

Trial and Error
The idea of using the immune system first drew significant research attention in the mid- to late-1990s, but multiple failures led to widespread discouragement, says Dr. Vonderheide.

Developments in recent years have produced the momentum that researchers believe will allow it to reach the next level of more powerful treatments and, ultimately, their combination with both traditional drugs and other immunotherapies, he says.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.