22 février, 2005 05:42

Thanks to Gina for sending us the following article...Myrl

Tricky Way to Fight Cancer

Thelma Imm's immune system is trained to pounce on the tiniest cold virus. Yet her body's natural defense network has failed to defeat a far more serious threat: kidney cancer that has spread to other organs.

For reasons that doctors don't yet fully understand, her immune cells don't seem to recognize the killers in their midst. Even the best treatment available -- a harsh regimen called high-dose interleukin-2 -- offers her only a slim chance of a cure.

So Imm, 77, is willing to try an unproven approach. In addition to the high-dose regimen, she'll receive an experimental vaccine designed to teach her immune cells to attack cancer the way they would any other threat.

''You just hope it works for you and, if not, that it works for someone else,'' says Imm, who is from Cleveland but stays with her daughter near Philadelphia during her treatments at Columbia Presbyterian Medical Center in New York. ''We've got to make progress.''

Traditional vaccines, such as those for polio or the flu, prevent disease by exposing the immune system to a weakened virus or portion of a virus. An experimental cervical cancer vaccine uses this strategy to protect against strains of a virus that cause that disease.

Therapeutic cancer vaccines, such as the kind given to Imm, work differently: They aim to treat existing disease by boosting the immune system. While vaccines may not be potent enough to melt large tumors, they may shrink smaller masses or eliminate traces of cancer that linger after surgery, says Jeffrey Schlom, chief of the tumor immunology and biology lab at the National Cancer Institute (NCI).

Although cancer vaccines haven't yet been approved by the Food and Drug Administration, several are being tested in large studies, and researchers hope that one or more will be widely available in a few years.

''It's an exciting time in the vaccine world,'' says Howard Kaufman, Imm's doctor and associate director of Columbia's cancer center. ''We have a much better understanding of the immune system, and we can manipulate it in ways that we couldn't imagine five years ago.''

Just last week, doctors announced results of the first trial showing a cancer vaccine can extend lives. The Provenge prostate cancer vaccine, made by Seattle-based Dendreon Corp., helped men with advanced disease who no longer benefit from standard hormone therapy live 4 months longer than patients who got placebos.

Experts say they're excited about newer technologies, still in early tests, that one day may work even better than Provenge.

But persuading the immune system to attack cancer cells has proved challenging, says David Avigan, director of bone marrow transplantation at Beth Israel Deaconess Medical Center in Boston. Unlike viruses or other invaders, cancer cells are made from the body's own tissues -- something the immune system is programmed not to attack, he says. Tumors also produce substances that tell the immune system to stand down.

Vaccines try to activate the immune system in different ways. Some focus on its foot soldiers, fighters called T-cells that destroy foreign substances, says Edgar Engleman, a professor of medicine and pathology at Stanford University School of Medicine. Many new vaccines aim higher up the chain of command, he says, targeting key immune players that order attacks, such as dendritic cells or other antigen-presenting cells.

Normally, when these cells spot an intruder, they break it up and isolate small markers, called antigens, that identify the substances as foreign. The cells then present these markers to T-cells and instruct them to kill anything bearing the same markers, Engleman says. But in cancer, immune cells may pass by tumors and do nothing.

To make the immune system more active, vaccines often include substances that act as stimulants, sending a sort of danger signal. But vaccines also need to be specific, to prevent a general immune system flare-up that could damage normal cells. That's why vaccines also introduce immune cells to a particular target: neutralized tumors or portions of tumors, such as genes, sugars, proteins or pieces of proteins.

Vaccines such as Provenge are tailor-made. They combine immune cells taken from the patient's own body with a marker commonly found on prostate cancer cells, Schlom says.

Personalized vaccines are expensive and time-consuming to produce, so many researchers prefer ''off the shelf'' vaccines, made with cells or proteins that are found in many cancers. These vaccines, such as one called PANVAC-VF, developed by NCI and a Massachusetts company, Therion Biologics, can be mass produced, says John Marshall, associate professor at Georgetown University Medical Center.

PANVAC-VF may have another advantage over older models. It targets not one, but two cancer markers, Marshall says. The markers are found on the majority of stomach, pancreas, colon, lung and breast tumors. ''If we win here, we may win in a lot of places,'' Marshall says.

Some scientists say aiming the immune system at one or two cancer markers may not be enough. Cancers have lots of potential markers, and most are unknown, says Elizabeth Jaffe, a professor at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore. Jaffe works with vaccines made from whole cancer cells, which may give immune cells more avenues of attack. To avoid reintroducing cancer to the body, she irradiates tumor cells, making them unable to divide, before injecting them into patients.

''The reason that there are all of these approaches is that nobody knows which one is going to work,'' says Philip Kantoff, a Harvard Medical School professor.

The vaccine being given to Imm, called Trovax, delivers its payload in an unusual vehicle: a vaccinia virus similar to one used in smallpox inoculations. Viruses prompt strong immune responses, Columbia's Kaufman says, making them a good way to introduce cancer-related genes to immune cells.

Once injected, viral vaccines either infect immune cells or are engulfed by them, Marshall says. Patients respond better if they get ''boosters'' made with a second virus called fowlpox, which doesn't multiply in humans. Doctors don't yet know how many boosters work best.

Cancer manipulates the immune system in ways that scientists are only beginning to understand. Some dendritic cells, for example, turn the immune response off, says Patrick Hwu, chairman of the melanoma medical oncology department at M.D. Anderson Cancer Center in Houston. Overstimulating the immune system could cause autoimmune reactions, in which the body attacks healthy tissue.

Cancers also are experts at camouflage. Like a pirate ship that takes down its black flag, cancers can hide the antigens that identify them as tumors, Kaufman says. Cancer cells also mutate frequently. It's possible that patients could become resistant to vaccines and require combinations of treatments.

Eduardo Garcia, 81, of San Ysidro, Calif., was diagnosed with prostate cancer 13 years ago. He joined a Provenge study four years ago after his cancer returned. The vaccine's only side effects were mild flu-like symptoms.

Recently, though, a tumor on Garcia's hip began growing again. His doctor has mentioned chemotherapy, but Garcia says he's not sure he wants to go through it.

''They've given me four years of my life,'' Garcia says. ''I'm not supposed to be here. I know it's a matter of time before this thing will grow back again, but I feel fine. I walk every day. I play with my dogs. For my age, I feel good.''

Researchers say they're encouraged by recent progress, but they note that cancer is always finding new ways to outsmart them.

''We've gone from a very poor shadow to a more precise understanding of how this works,'' says Alan Houghton, chief of clinical immunology at Memorial Sloan-Kettering Cancer Center in New York. ''We still have an awful lot to learn.''

Source: USA TODAY