Pairing one of the new tumor-starving drugs with a vaccine that
boosts the body's immune system delivers a two-pronged attack on
cancer that is much more effective than the much-touted drug alone,
suggests a new study in rodents.
University of Pittsburgh researchers found that the combination
of the drug endostatin and the vaccine would not simply slow or
shrink tumors as endostatin alone does, but destroys the tumors
outright.
Endostatin, the much-anticipated cancer treatment currently
undergoing its first testing in humans, is a powerful natural
substance which, in animal experiments, has dramatically shrunk
tumors by attacking the blood vessels that grow in an around them.
Such drugs, called angiogenesis inhibitors, can slow the growth
of cancers and sometimes even shrink tumors. But, since they attack
the blood vessels, and not the tumors themselves, these inhibitors
often leave small pockets of cancer cells that can regrow when the
drug is stopped, said Eli Gorelik, a cancer researcher at the
University of Pittsburgh.
Gorelik said a combination of endostatin and a vaccine-like
substance that sparks the immune system has completely eradicated
lung tumors in four of eight mice - one of several small groups of
rodents on which the treatment has been tested.
``We have the first data suggesting that anti-tumor
immunotherapy combined with (blood vessel) inhibition is a
promising treatment strategy for cancer,'' said Gorelik.
Dr. Judah Folkman of Harvard Medical School and Children's
Hospital in Boston, in whose lab endostatin was discovered, called
the findings ``a very nice and very important advance.''
Gorelik gave a report on the work over the weekend at the Era of
Hope meeting in Atlanta that showcased projects funded by the U.S.
Department of Defense, which supports breast cancer research.
In addition, Gorelik said an article on the research findings
has been submitted to a cancer research journal.
Endostatin, angiostatin and other angiogenesis inhibitors
pioneered by Folkman have shown in animals they can choke off
tumors' blood supply, halting their growth and in some cases
forcing them to shrink.
But often, when the drug is stopped, the tumors grow back,
because some of the blood supply is able to survive. Under the
microscope, ``small pockets of tumor cells remain,'' said Gorelik
in an interview.
``So, we therefore need to stimulate the immune system to attack
the tumor cells in order to destroy and completely eradicate
them,'' Gorelik said.
In the animal experiments, the spark to the immune system was
provided by lung cancer cells that carry molecules on their surface
that the animals' immune system treats as hostile invaders. In some
of the experiments, the spark came from their own lung tumors
(which had been implanted into them), and, in others, the lung
cancer cells were injected like a vaccine.
Gorelik said that, in one small group of animals, half of them
``became well, with complete and permanent regression of tumors,''
for at least six months. By contrast, no tumors regressed in mice
that had gotten only endostatin or only received the tumor cell
vaccination.
Both the tumor-starving drugs and the immune system vaccines
appear to be far less toxic than the standard chemotherapy drugs
that are the backbone of today's cancer therapies. But both groups
of treatments - angiogenesis inhibitors and cancer vaccines -
remain unproven in humans.
Folkman has long predicted that angiogenesis inhibitors like
endostatin will be most effective when combined with other
angiogenesis inhibitors or with chemotherapy or radiation.
This new report, he said, ``is an exciting step'' because ``it
means that anti-angiogenic therapy can eventually be added to
immunotherapy, and he's got some real data.''
Gorelick added that a large number of human trials of immune
system therapy and angiogenesis inhibitors are now in progress. The
new findings, he said, should lead to designing clinical trials
that combine the two weapons.
Endostatin is being developed as a drug by EntreMed Inc., a
Maryland biotechnology company.
