1-Proteins: Cancer Vaccines: Decades of failure haven't extinguished hope

[GENET <coordination@genet-info.org>]

                                 PART I
------------------------------- GENET-news -------------------------------

TITLE:  Cancer Vaccines: Decades of failure haven't extinguished hope
SOURCE: The Miami Herlad, USA, by Jacob Goldstein
        http://www.miami.com/mld/miamiherald/living/13222581.htm
DATE:   22 Nov 2005

------------------ archive:  http://www.genet-info.org/ ------------------


Cancer Vaccines: Decades of failure haven't extinguished hope

The history of cancer vaccines is a history of failure.

For 20 years, scientists have dreamed of creating vaccines that teach the
body to destroy tumors. Yet after hundreds of clinical trials, not a
single vaccine has been approved to treat cancer.

''The whole field . . . was riddled with these high expectations,'' says
Jill O'Donnell-Tormey, who directs the nonprofit, New York-based Cancer
Research Institute, a longtime funder of vaccine trials. ``Then everybody
failed.''

Yet everybody is still trying. There are at least six cancer vaccine
trials planned or under way in South Florida, and more than 100 other
trials around the country. Their goal is not to prevent cancer, but to
treat it -- to stimulate the body to attack cancers of the skin,
prostate, pancreas, breast and lungs, to name a few.

Which raises an obvious question: Why?

Why pour millions of dollars into scores of vaccines tested on thousands
of patients for an idea that has consistently disappointed?

As much as anything, the answer comes down to the elegance of the idea.

The three ways doctors treat cancer now -- surgery, radiation,
chemotherapy -- are brutal, aggressive approaches that can cause
permanent harm or even death. The ideal vaccine, by contrast, would nudge
the body to heal itself -- an advance that could reduce the cutting,
burning and poisoning that now comprise the anti-cancer arsenal, says Dr.
Steven Burakoff, director of the New York University Cancer Institute.

''If you want to think about the optimal therapy,'' he says, ``. . .
think about the possibility of mobilizing our own immune system to do
something about cancer.''

Last month, researchers announced a successful trial of an experimental
vaccine that may prevent cervical cancer. The vaccine, being developed
under the brand name Gardasil, could reach the market next year and save
hundreds of thousands of lives. But in the world of cancer vaccines, the
cervical cancer vaccine is an aberration.

Cervical cancer is one of very few cancers that is caused by a virus; the
vaccine prevents cancer by preventing the virus from taking hold in the
body. The vaccine, therefore, can't be used for anyone who already has
cervical cancer.

Vaccines capitalize on the body's innate ability to detect and destroy
invaders. A vaccine is a pseudo-invader, usually a slightly altered
version of a disease-causing virus. The body responds to a vaccine by
building custom-made cells whose sole purpose is to attack the pseudo-invader.

Some of those cells remain in the system long after the vaccine pseudo-
invaders have been destroyed. If the real invader -- the virus -- shows
up, the cells swarm and attack, destroying the virus before it can harm
the body.

Even in the absence of a vaccine, the immune system is usually able to
fight off infection. You get a cold (or the chicken pox, or the flu), and
then you get better.

There is evidence that the immune system naturally attacks some nascent
cancers as well, Burakoff says.

In patients whose immune systems have been decimated by AIDS, the rate of
certain cancers increases dramatically -- suggesting that in healthy
patients, the immune system destroys many would-be cancers before they
grow to noticeable size.

And researchers have found immune cells known as killer T-cells attacking
cancer in some patients. In the early 1980s, scientists identified a
melanoma antigen -- a protein that was on the surface of cancerous
melanoma cells, but not, by and large, on healthy cells.

This discovery gave rise to a wave of optimism: Immunologists believed
they could use a vaccine to strengthen the immune system's natural
response and cure melanoma, a deadly form of skin cancer.

It wasn't so simple.

''Twenty years ago, when people announced immunology would conquer
cancer, people didn't realize how little they knew about the immunology
of cancer,'' says Dr. Jose Lutzky, director of the melanoma program at
Mount Sinai Medical Center in Miami Beach. ``Tumors . . . evade the
immune system by producing proteins that make them invisible. If a
vaccine has a target on the tumor, the tumor can make the target disappear.''

But, in a molecular game of cat and mouse, discovering these complexities
has inspired researchers to create ever more complex vaccines.

Most new vaccines add molecules to incite a stronger immune response.
Some use genetically modified whole cancer cells. Others block a compound
that tells the immune system to stop making T-cells.

The scientists say their increasing understanding of the immune system
will lead to improved vaccines.

''I really think we're doing better now,'' Lutzky says. ``I could be
wrong, but I don't think so.''



                                 PART II
------------------------------- GENET-news -------------------------------

TITLE:  A close look at cancer vaccines
SOURCE: The Miami Herlad, USA, by Jacob Goldstein
        http://www.miami.com/mld/miamiherald/living/13222577.htm
DATE:   22 Nov 2005

------------------ archive:  http://www.genet-info.org/ ------------------


A close look at cancer vaccines

Among the cancer vaccines being tested or developed in South Florida:

- A prostate cancer vaccine in late-stage trials is customized for each
patient. Doctors take a blood sample from the patient and isolate
specialized immune system cells known as antigen-presenting cells. In the
body, these cells bind with invaders, then train T-cells to attack the
invaders.

To create the vaccine, the patient's antigen-presenting cells are
combined in the lab with an antigen that exists on the surface of
prostate cancer cells.

- Scientists recently gained insight into a new immune system molecule
called CTLA-4 that slows the activity of T-cells. Some melanoma patients
in experimental trials are being treated with both a vaccine and a
compound that blocks CTLA-4.

- A lung cancer vaccine developed by Dr. Eckhard Podack and his
colleagues at the University of Miami uses whole tumor cells, genetically
modified to stimulate the immune system.

Some researchers believe whole cells may be more effective than
individual antigens. The cells are irradiated, so they do not cause new
cancers in the body.

An early trial showed that patients' immune systems respond to the
vaccine, but more research must be done to determine whether the vaccine
will improve survival, Podack said.

- A breast cancer vaccine in preliminary trials is designed to prompt the
immune system to attack the cancer protein Her-2, the same protein
targeted by the cancer drug Herceptin, which was recently shown to reduce
the risk of recurrence for some women.

Like many new vaccines, this one includes not only the antigen, but also
an adjuvant -- a molecule that intensifies the immune system's response.
The adjuvant is based on a toxin produced by a common family of bacteria.

''I feel lucky, but at the same time it's scary, '' said Renee Barrera, a
South Miami woman who is a patient in the trial. ``It's an experiment,
and you don't really know what's going to happen.''


FOR MORE INFORMATION

The following resources list clinical trials of cancer vaccines and other
experimental therapies:
- The National Cancer Institute: www.cancer.gov, 800-4-CANCER
- The Florida Clinical Trials Cooperative: http://
www.floridacancertrials.com, 800-584-9976




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