Cancer vaccines make progress

Cancer vaccines make progress

A vaccination against cancer may still be the stuff of science fiction, but some biotechnology companies believe they can invent a vaccine to spur the body's immune system into rejecting cancer cells.

"Harnessing the immune system to fight cancer has been a great theory for a long time, but cancer is very, very different than other diseases. There have been a number of failures and a lot of skepticism," said David Tousley, chief operating officer at Avax Technologies Inc., which last year launched a skin cancer vaccine in Australia.

Vaccines for diseases such as chicken pox or the flu use a weakened or killed pathogen to stimulate antibody production against the disease without causing severe infection. In the case of cancer, the idea is to immunize patients against substances on their cancer and to educate the immune system to attack those cells and no others.

"The big hope is not just for the same kind of vaccine that works against a virus but of using modern knowledge to treat with the body's own immune system," said T.J. Koerner, the American Cancer Society's scientific program director.

Being able to destroy cancer cells preemptively when they are only in small colonies - before they have spread - would have an enormous benefit compared to treating a grown tumor or cancer cells that are circulating through the body, he said.

Koerner emphasized that cancer is a disease of multiple forms and each type, and possibly each tumor, would have to be treated with a separate vaccine. None of the vaccines are being tried in people who have never had cancer.

"We're seeking a means of turning patients' immune systems against tumors," said David Urdal, chief scientific officer at Dendreon Corp.

Companies like Avax and Dendreon are working on novel ways to vaccinate patients who already have cancers such as lung, skin, prostate and breast against the disease. Most vaccines are still in the experimental stage but some are being sold overseas and others are being tested in pivotal clinical trials.

Seattle-based Corixa Corp. last month began sales in Canada of its vaccine Melacine for treatment of advanced skin cancer. Corixa's approach to vaccines involves identifying tumor proteins that induce a response from the immune system.

Canadian regulators approved Melacine based on clinical trials showing it was safer and less toxic than standard chemotherapy in treatment of Stage IV melanoma - a lethal form of skin cancer - even though there was no big difference in effectiveness.


"It's a better alternative than losing your hair and throwing up," Corixa spokesman Jim DeNike said.

He said Corixa and trial investigators are compiling follow-up data from another trial of Melacine in patients with Stage II melanoma and plan, depending on the results, to use that data for a U.S. marketing application this year.

"Results from the Stage II patients showed that Melacine was able to strengthen and boost their immune systems. If you're in Stage IV melanoma, your immune system is so beaten down there is less effect," DeNike said.

Corixa also has earlier-stage trials underway for vaccines to treat breast, ovarian and pancreatic cancer.

Last year, Missouri-based Avax began sales in Australia - the world leader in per-capita incidence of melanoma - of its customized skin-cancer vaccine M-Vax as a treatment for Stage III melanoma that has spread to lymph nodes.

Avax uses radiation to kill cells from a patient's actual tumor, then alters them chemically so the immune system recognizes them as foreign when the vaccine is injected. Since each vaccine is customized to an individual patient it is more powerful than a mass-produced vaccine, Avax says.

"We use the patient's own cells to awaken the immune system, not just one or two proteins. It's unlikely that cancer is going to be treated with a generic antigen," Tousley said.

Trial results show a 55-percent survival rate after five years for patients with advanced skin cancer who got the 8-dose M-Vax regimen, compared with a historic 20-percent survival rate for patients who undergo surgery, the company said.

The fact that a vaccine needs to be able to contain and eliminate any new cancer cells as well as mutated cells makes fighting cancer through a vaccine very different than an inoculation against a virus like smallpox, Tousley said.


In the United States, Avax is conducting a pivotal trial of M-Vax in Stage III melanoma and a mid-stage trial for Stage IV skin cancer. The company also has an ovarian cancer vaccine, O-Vax, in a mid-stage trial and said it is evaluating its technology in cancers including leukemia and breast cancer.

Avax said it hopes to launch M-Vax in parts of Europe later this year and in the United States by late 2003.

Dendreon is another Seattle company seeking to combat cancer through immunotherapy, particularly in patients who have undergone conventional therapies but still have some residual cancer. Its most advanced product is Provenge, a drug for prostate cancer currently in late-stage clinical trials.

The company believes the key to directing the immune system to fight cancers is to manipulate dendritic cells - a specialized class of immune system cells - to stimulate T-cells to eliminate cancers and virally infected tissue.

In addition to Provenge, Dendreon is conducting early clinical trials of a potential vaccine for B-cell malignancies, including multiple myeloma or blood cancer, and has additional therapeutic vaccines in preclinical development for the treatment of other common malignancies.

New York-based ImClone Systems Inc. has developed an experimental antibody, BEC2, designed to prevent or delay the recurrence of certain types of tumors when used with an immune stimulant. The BEC2 antibody mimics a tumor antigen on the surface of certain types of tumor cells, which appears to stimulate a stronger immune response to cells that naturally express the antigen, the company said.

ImClone is currently evaluating BEC2 in a late-stage clinical trial as a treatment for limited stage small cell lung cancer. The vaccine is also being studied in patients with extensive small cell lung cancer and malignant melanoma.

Antigenics Inc. recently moved its cancer vaccine candidate, Oncophage, into late-stage clinical trials for kidney cancer. The vaccine is based on the company's technology for using heat shock proteins to activate immune responses.

HSPs are a family of proteins present in all cells whose expression is triggered by physiological stresses such as a rise in temperature. HSPs are required for cellular metabolism and help repair cells damaged by heat or other stresses.

In tumor cells and pathogen-infected cells, HSPs associate with peptides specific to the tumor or pathogen, and there is evidence that HSPs help the immune system to recognize the invaders and eliminate abnormal cells, Antigenics says. ( ).

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