Immunological Research: A multi-faceted approach to curing disease

[gdpawel]

The potential to harness the body's immune system to fight cancer may finally prove itself on a large scale in the next couple of years. Scores of new immunotherapy vaccines and other immune system modifiers are being tested against a variety of cancers. At least a dozen therapies are set to have key late- or mid-stage trial data.

The concept of using the immune system against cancer dates back to the 1890s when Dr. William Coley, a New York surgeon, noted that some patients who got infections after cancer surgery fared better. He surmised that the immune response triggered by the infection was also working to eradicate cancer.

According to Dr. Glenn Dranoff, co-director of the Dana-Farber Cancer Vaccine Center in Boston, although the idea of a vaccine or cancer immunotherapy has been around really for at least 100 years, we now know a lot more about what are the requirements to generate an effective anti-cancer immune response than we ever did.

Researchers had previously believed that only melanoma and kidney cancer had the right properties to respond to immune system therapy. They were eventually proven wrong. Clinical trials now are taking on lung, breast, liver, prostate, pancreatic, ovarian, head and neck and brain cancers.

The basic idea remains the same: train a patient's immune system to attack the cancer. But new approaches based on more recent knowledge of the immune system's components include activating a variety of cells to go after tumors and modifying mechanisms that keep either the immune system in check or turn it loose.

There appears to be near universal agreement that to achieve optimal benefit, immunotherapies should be combined with targeted cancer drugs or other immunotherapies in a multi-pronged attack.

According to the researchers at Anderson, our immune cells are like little tanks that travel round the body to shoot bacteria and viruses that are hurting us, but you can't let them go unregulated. When the body has cancer you want the tanks to go a little bit wild, so they want to lift those brakes and let them go after the enemy.

Some believe that companies would do well to test immunotherapies at an earlier stage of the disease, perhaps to prevent recurrence. Such trials take years longer to produce results, so companies tend to start trials with advanced cancer patients with limited life expectancy that yield results sooner.

The body's immune system is constantly trying to keep tumors from forming or coming back. If you can give the immune system a boost in terms of helping out with that long-term surveillance, it could make more sense biologically.

The immune system may take some months to ratchet up its anti-cancer armaments researchers say, so giving immunotherapy to a patient with just a few months to live may be futile.

Early disappointment in the field may have been due to testing on patients with very advanced disease whose immune systems were severely compromised by chemotherapy and radiation, and such failures are to be expected.

[gdpawel]

An old idea for treating cancer is yielding impressive results on cancer patients—and lots of attention from drug companies.

New medicines that shrink tumors and have beneficial effects lasting for months to years in some cancer patients are helping breathe new life into an old idea: using a patient’s own immune cells to attack malignant cells.

Several drug makers are trying to prove the safety and efficacy of new medicines that harness the body’s own lines of defense. Merck, for one, is testing an immune-modulating compound in patients with metastatic, or spreading, melanoma. In an early-stage trial, half of the patients receiving the highest-attempted dose of the drug saw their tumors shrink or disappear, and more than a year later, the vast majority of those patients who responded to that dose and lower doses were still alive. On average, the prognosis for survival a patient with late-stage metastatic melanoma is less than a year.

“This is not a garden-variety cancer treatment development program,” says Roger Perlmutter, an immunologist who heads R&D at Merck. “This looks special at this stage,” he says.

Merck’s compound is an antibody, a Y-shaped biological molecule that grabs onto a specific protein. The target protein normally prevents immune cells from attacking cancer. By blocking the activity of that protein, the antibody frees the immune cell to fight the disease. Roche, GlaxoSmithKline, Bristol-Myers Squibb, and others are also developing antibodies to release such brakes on the immune system.

New details of how these compounds work and for whom will be presented by many groups involved in the new push for cancer immunotherapy at this year’s American Association for Cancer Research meeting, in San Diego. The conference, which started on Saturday, is the largest meeting of oncologists and oncology researchers in the world. Although researchers express excitement about the potential for immune-modulating medicines to combat cancer—some experts even use the word “cure”—many caution that it will take time to fully understand how well the treatments are working.

Just a few years ago, many in the biomedical community would have been skeptical. Numerous attempts to induce the immune system to attack cancer had proved ineffective in humans, says Charles Link, CEO of New Link Genetics, a biotech company that has been developing immunotherapies for years. “But as the sophistication of our understanding of immunology increased, new strategies evolved to attack the disease, and those strategies are turning out to work in the clinic,” says Link.

“It is exciting—we have been working on this for so long, and now finally human results show it clearly works,” says Jianzhu Chen, a biologist at the Koch Institute for Integrative Cancer Research at MIT, who studies cancer immunotherapy. “This will have a major impact on cancer treatment.”

In 2011, Bristol-Myers Squibb began to sell Yervoy, also an antibody, which was the first marketed medicine to disrupt the process that prevents immune cells from attacking cancer. The treatment has shown to nearly double the survival rate of metastatic melanoma patients, enabling 20 percent of patients to live up to four years after diagnosis. The clinical trial of Yervoy was the first ever to show that life could be extended for advanced melanoma patients.

The antibody medicines represent just one part of the renaissance of cancer immunotherapy. There’s also been progress in a form of cellular therapy that engineers a patient’s own immune cells to better recognize cancer cells, after which they are infused back into the patient. Other companies, such as Amgen, are developing virus-based gene therapies that selectively kill cancer cells while simultaneously making the cells better targets for the immune system.

The immune system can be a powerful ally for doctors, but they must tread carefully. “We know the immune system is capable of killing any cell. If we aren’t careful, we could trigger systemic autoimmune disease of major consequences,” says Perlmutter. “We have to take advantage of the enormous potential of immune recognition and response and at same time leave ourselves in a position where we can control that activity,” he says.

So far, the treatments have been tested on only a subset of cancer types—mostly melanoma but also lung cancers and breast cancers, among others. Researchers will have to test the treatments on more cancer types to know how wide a range of malignancies they can attack, and whether certain targets, or even combination of targets, are needed. “It may be that in different tumor types, different immune modulators will have different importance,” says Deborah Law, who heads one of Merck’s biologics research units. “Combination approaches might be most effective,” she says.

Citation: The Revival of Cancer Immunotherapy. Susan Young Rojahn. MIT Technology Review. April 7, 2014