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Senior Citizen Health & Medicine
Vaccination with Embryonic Stem Cells Prevents Lung
Cancer in Mice
Announced day after Democrats win pledging more
stem cell research
 November 8, 2006 On the day after Democrats had
big election gains in the Congress, partially on a pledge to fund stem
cell research, it was announced that researchers have vaccinated mice
with embryonic stem cells and prevented lung cancer, the biggest cancer
killer. They say this suggests it could be possible to develop embryonic
stem cell vaccines that prevent cancers in humans, such as hereditary
breast and colon cancer and lung cancer caused by smoking or other
environmental factors.
The animals had had cancer cells transplanted into
them after the vaccination or were exposed to cancer-causing chemicals.
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Health & Medicine |
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Professor John Eaton told a news briefing at the
EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in
Prague today: "We found that the vaccinations were between 80-100%
effective in preventing tumor growth in mice that were subsequently
challenged with transplanted Lewis lung carcinoma, and it was between
60-90% effective in mice subsequently exposed to carcinogens that cause
lung cancer.
"Our results raise the exciting possibility of
developing a prophylactic vaccine capable of preventing the appearance
of various types of cancers in humans, especially those with hereditary,
chronological or environmental predispositions to neoplastic disease."
However, he warned that the work was still in its
early stages and that people should not think that, for instance, they
could start, or carry on, smoking because a vaccine to prevent lung
cancer was just around the corner.
"Cancer has been prevented and even cured in mice
hundreds of times. At present, all I can say is that so far it looks
good, and that, unless something unexpected happens, this strategy might
some day be applied to humans at high risk for development of cancer.
"The likelihood of this happening is more a
question for the US Food and Drug Agency than for us. Given their
stringent regulations I consider it quite likely that, by the time this
is tried in humans, I will be pushing up daisies."
Prof Eaton is the James Graham Brown Professor of
Cancer Biology and Deputy Director of the James Graham Brown Cancer
Center, University of Louisville, USA. He and his colleague, Dr Robert
Mitchell, tested two different vaccines in the mice.
One consisted of embryonic stem cells (ESC) only,
obtained from mouse blastocysts (very early, pre-implantation embryos).
The other vaccine consisted of the ESCs combined
with cultured fibroblast cells producing GM-CSF, a growth factor usually
made by white blood cells and blood vessel-lining endothelial cells,
which "supercharges" the immune response and appears to enhance the
vaccine-induced immunity to cancer.
Prof Eaton explained: "We needed a delivery vehicle
for GM-CSF and chose STO fibroblasts because they are often used as a
'feeder layer' to maintain these particular mouse embryonic stem cells
in their embryonic state. If we had used only ESCs expressing GM-CSF,
they might have differentiated into non-embryonic cells, which,
therefore, would not have worked as a vaccine."
He and his team injected mice with ESCs alone or
ESCs + STO/GM-CSF. In mice that had Lewis lung carcinoma transplanted
into them afterwards, ESCs were 80% effective in preventing tumour
growth and ESCs + STO/GM-CSF were 100% effective.
In mice subsequently exposed to a carcinogen that
causes lung cancer (3-methylcholanthrene followed by repetitive dosing
with butylated hydroxytoluene), ESCs resulted in 60% of mice remaining
tumour free after 27 weeks and ESC + STO/GM-CSF resulted in 90%
remaining tumour free. Importantly, tumours arising in vaccinated mice
were, on average, about 80-90% smaller than tumours in unvaccinated
mice.
All the unvaccinated mice developed tumors. None of
the vaccinated mice developed autoimmune disease or a showed a
significant decline in adult pluripotent bone marrow stem cells both
potential adverse responses to the vaccinations.
Prof Eaton said, "We think the results from the
carcinogen-initiated cancers are probably the most important, as they
are closer to the 'real-life' model of the development of cancer than
just implanting cancer cells in an animal. We are studying several
different types of carcinogen-induced mouse cancers (skin, colon,
breast) to determine whether the preventative effect of vaccination
extends beyond our models of lung cancer (although in our state of
Kentucky with its high smoking rates, lung cancer alone would be a big
victory). We may also vaccinate ageing rodents, the majority of which
develop endocrine tumors in old age.
"In terms of human testing, if all goes well, then
I think this vaccination might best be tested in women at high (genetic)
risk of breast cancer, in people with high (genetic) risk of colon
cancer and, perhaps, in smokers.
"Our progress over the next few years will depend,
to a large extent, on whether we can attract significant funding. Our
work is presently supported by a pilot grant from our cancer centre and
a small grant from the Kentucky Lung Cancer Research Program. US federal
funding agencies such as the NIH notorious for funding predictable
research have been quite disinterested."
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