X-Message-Number: 18736
From: "Peter Christiansen" <>
Date: Sat, 9 Mar 2002 12:32:44 -0600
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Novel vaccine combats cancer
Gene-engineered approach targets only tumor cells
By Charlene Laino
MSNBC
Feb. 5 A genetically engineered vaccine that activates the patient s
own immune system to attack and destroy tumors is showing promise for the
treatment of prostate cancer. More importantly, the novel strategy holds the
potential to stop the spread of all types of cancer, researchers say.
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THE CONCEPT IS SIMPLE: Use the body s own disease-fighting soldiers
so-called killer T-cells to attack a tumor. Early results show
the tactic is working.
In a preliminary trial of the so-called dendritic cell vaccine in 13
patients with prostate cancer who had exhausted all the usual
life-extending treatments, there were no adverse side effects.
Additionally, immunological testing indicated that the vaccine revved up
the patient s immune system to fight the cancer, says Dr. Johannes
Vieweg, an associate professor of urology and assistant professor of
immunology at Duke University Medical Center in Durham, N.C., and senior
investigator of the study.
And while this just-published work was done in prostate cancer patients,
similar results have since been observed in kidney cancer patients as
well, Vieweg says.
In fact, this approach extends the scope of vaccination to virtually
every cancer patient, regardless of his type of tumor or its genetic
makeup, he adds.
WAVE OF FUTURE
As many in the field believe, targeted vaccines appear to be the wave of
the future.
Dr. Michael Gordon, an oncologist at the Arizona Cancer Center in Tucson,
calls them a huge leap beyond other types of cancer vaccines, which
had shown no clinical benefits.
What is particularly exciting, Gordon says, is that the vaccines can be
customized to each patient and his or her particular type of cancer.
We re very excited, he says. Such targeted therapies are the
future of cancer treatment.
The strategy grew out of a new understanding of how our immune systems
react to cancer cells. While the immune system exists, in essence, to
recognize outside invaders and attack them, it often has trouble
distinguishing normal cells from cancerous ones since both arise from our
own tissue.
Tumor cells are tricky, and have found ways of hiding their abnormal
surface proteins making themselves, in effect, nearly invisible to
the immune system, says Dr. Lawrence Fong, a cancer researcher at
Stanford Medical School in Palo Alto, Calif., whose work on dendritic
vaccines is considered seminal.
But in recent years, researchers realized that they could take advantage
of genetic engineering to wake up a slumbering immune system to the fact
that tumor cells have invaded the body.
Once they recognized the cancer cells as the enemy, the immune system s
T cells would do their job and attack, they reasoned.
And they were right.
NOVEL APPROACH
In the latest approach, a team led by Vieweg took advantage of a rare but
integral part of the immune system known as the dendritic cell. A
dendritic cell is a type of white blood cell that activates the immune
system by capturing antigens substances that trigger immune responses
against viruses, bacteria and tumors and presenting them to T-cells.
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To create the vaccine, genetic engineering was employed to fuse immature
dendritic cells with RNA from prostate-specific antigen (PSA) from the same
patient. PSA is a protein that is secreted by the prostate gland and is often
elevated in prostate cancer. The hybrid was then injected back under the patient
s skin as well as intravenously.
In the trial, 13 men with prostate cancer that was continuing to spread
despite standard treatment with hormones were given three escalating
doses of the vaccine.
The results were published in the February issue of the Journal of
Clinical Investigations.
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Overall, the vaccine was well-tolerated. Four subjects developed
low-grade fevers and flu-like symptoms, and four patients had
inflammation at the site of the injection that subsided after two to
three days.
The researchers then performed immunological tests to ensure that T-cells
were functioning and able to kill tumor cells, in addition to tests to
determine whether the T-cell levels rose.
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In all 13 participants, the researchers detected a dramatic increase in
PSA-specific T-cells, suggesting the vaccine was successful in boosting
the immune system and turning T-cell attention to the cancer at hand.
A second test showed that these T-cells can actually kill tumor cells, he
adds. We took T-cells from the patient and incubated them with tumor
cells and showed killing in the test tube, he says.
Simply showing an increase in number of T-cells doesn t prove the
immune system is actively attacking the tumor, but this latter test does,
Vieweg explains.
Immunological data, which is sometimes not collected in such trials, is
highly important in proving that the cancer vaccine is working in the
patient and other influences are not at work, according to Vieweg.
Some studies examine only if there is a reduction in tumor growth, but
this would only show part of the story, he said. You wouldn t
see the changes in the body that might indicate that a vaccine is
promising.
The Duke study was not designed to determine whether cancer was
eradicated, but a little impact was seen, he says. In six of seven
patients, PSA progression was slowed. (The other six patients were
excluded from this part of the analysis because they underwent additional
treatments that could impact PSA levels.)
In patients with disease so advanced, to see any effect on PSA is
huge, Vieweg says.
The next step for prostate cancer, Vieweg says, is to give the vaccine to
patients who have just had their prostates removed but in whom some
lingering cancer cells remain.
Since the disease is at a much earlier stage, we expect we will see an
actual lowering of PSA levels as well as better control of cancer
cells, says Vieweg, adding that he just got official approval for
such a study.
BRANCHING OUT
In the meantime, though, Vieweg isn t sitting still. He s already
branched out and has just completed a study of a more potent version of
his vaccine in patients with kidney cancer.
The idea, he says, is to use fully mature dendritic cells and program
them to carry multiple tumor antigens rather than just PSA. This involves
using RNA from the whole tumor rather than from PSA or another
cancer antigen to create the vaccine.
While Vieweg is not free to share the details of the kidney cancer trial
pending publication in a medical journal, the results were very
interesting, very encouraging, he says.
Eventually, he hopes the approach will prove successful for all types of
cancer. Meanwhile, other researchers are employing similar strategies; in
May, for example, Fong reported early success with another type of
dendritic vaccine in colorectal and lung cancer patients.
The beauty of all these approaches is that the vaccines boost the
immune system, rather than beat it up like chemotherapy, Vieweg
says.
And use of RNA from the whole tumor will make them far more user-friendly
helping cancer patients regardless of what type of tumor or genetic
makeup.
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