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Vaccine against HER2-positive Breast Cancer
offers complete protection in lab
Newswise — Researchers at
Wayne State University have tested a breast
cancer vaccine they say completely
eliminated HER2-positive tumors in mice -
even cancers resistant to current anti-HER2
therapy - without any toxicity.
The study, reported in the
September 15 issue of Cancer Research, a
journal of the American Association for
Cancer Research, suggests the vaccine could
treat women with HER2-positive,
treatment-resistant cancer or help prevent
cancer recurrence.
The researchers also say it
might potentially be used in cancer-free
women to prevent initial development of
these tumors.
HER2 receptors promote normal
cell growth, and are found in low amounts on
normal breast cells.
But HER2-positive breast
cells can contain many more receptors than
is typical, promoting a particularly
aggressive type of tumor that affects 20 to
30 percent of all breast cancer patients.
Therapies such as trastuzumab
and lapatinib, designed to latch on to these
receptors and destroy them, are a mainstay
of treatment for this cancer, but a
significant proportion of patients develop a
resistance to them or cancer metastasis that
is hard to treat.
This treatment relied on
activated, own-immunity to wipe out the
cancer, says the study’s lead investigator,
Wei-Zen Wei, Ph.D., a professor of
immunology and microbiology at the Karmanos
Cancer Institute.
“The immune response against
HER2-positive receptors we saw in this study
is powerful, and works even in tumors that
are resistant to current therapies,” she
said.
“The vaccine could
potentially eliminate the need to even use
these therapies.”
The vaccine consists of
“naked” DNA – genes that produce the HER2
receptor – as well as an immune stimulant.
Both are housed within an
inert bacterial plasmid. In this study, the
researchers used pulses of electricity to
deliver the injected vaccine into leg
muscles in mice, where the gene produced a
huge quantity of HER2 receptors that
activated both antibodies and killer T
cells.
“While HER2 receptors are not
usually seen by the immune system when they
are expressed at low level on the surface of
normal cells, a sudden flood of receptors
alerts the body to an invasion that needs to
be eliminated,” Wei said.
“During that process, the
immune system learns to attack cancer cells
that display large numbers of these
receptors.”
They also used an agent that,
for a while, suppressed the activity of
regulatory T cells, which normally keeps the
immune system from over-reacting.
In the absence of regulatory
T cells, the immune system responded much
more strongly to the vaccine.
Then, when the researchers
implanted HER2-positive breast tumors in the
animals, the cancer was eradicated.
“Both tumor cells that
respond to current targeted therapies and
those that are resistant to these treatments
were eradicated,” Wei said.
“This may be an answer for
women with these tumors who become resistant
to the current therapies.”
Wei’s lab is the first to develop HER2 DNA
vaccines, and this is the second such
vaccine Wei and her colleagues have tested
more extensively.
The first, described in a
study in 1999, formed the model of a vaccine
now being tested by a major Pharmaceutical
company in early phase clinical trials in
the U.S. and in Europe in women with
HER2-positive breast cancer.
In order to ensure complete
safety, Wei says the current test vaccine
uses HER2 genes that are altered so that
they cannot be oncogenic.
The receptors produced
do not contain an “intracellular domain” –
the part of the receptor that is located
just below the cell surface and transmits
growth signals to the nucleus.
"The
first vaccine was also safe, she says, but
contained a little more of the native HER2
receptor structure. “With this vaccine, I am
quite certain the receptor is functionally
dead,” she said.
“The greatest power of
vaccination is protection against initial
cancer development, and that is our ultimate
goal with this treatment,” Wei said.
The mission of the American
Association for Cancer Research is to
prevent and cure cancer.
Founded in 1907, AACR is the
world’s oldest and largest professional
organization dedicated to advancing cancer
research.
The membership includes more
than 28,000 basic, translational and
clinical researchers; health care
professionals; and cancer survivors and
advocates in the United States and 80 other
countries.
AACR marshals the full
spectrum of expertise from the cancer
community to accelerate progress in the
prevention, diagnosis and treatment of
cancer through high-quality scientific and
educational programs.
It funds innovative,
meritorious research grants.
The AACR Annual Meeting
attracts more than 17,000 participants who
share the latest discoveries and
developments in the field. Special
conferences throughout the year present
novel data across a wide variety of topics
in cancer research, treatment and patient
care.
AACR publishes five major
peer-reviewed journals: Cancer Research;
Clinical Cancer Research; Molecular Cancer
Therapeutics; Molecular Cancer Research; and
Cancer Epidemiology, Biomarkers &
Prevention.
Its most recent publication
and its sixth major journal, Cancer
Prevention Research, is dedicated
exclusively to cancer prevention, from
preclinical research to clinical trials.
The AACR also publishes CR, a
magazine for cancer survivors and their
families, patient advocates, physicians and
scientists. CR provides a forum for sharing
essential, evidence-based information and
perspectives on progress in cancer research,
survivorship and advocacy.
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