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the first time, scientists have shown that a new type of immunotherapy can
reach and treat brain cancer from the bloodstream in mice. The nano-immunotherapy
stopped brain tumor cells multiplying and increased survival.
Scientists who devised an immunotherapy that can cross the blood-brain barrier in mice hope that the findings may one day translate to humans.
The researchers believe that the new
treatment could be the key to improving survival in people with glioblastoma,
the most common and aggressive type of brain cancer.
A recent Nature Communications paper describes how they
combined advances in nanotechnology and immunotherapy to deliver checkpoint
inhibitors across the blood-brain barrier.
Checkpoint
inhibitors are drugs that help the immune system fight cancer. In the new
immunotherapy, the drugs can remove a mechanism that enables the brain tumor to
withstand attack from cancer-killing cells.
The blood-brain barrier is a unique feature of the vessels that supply blood to the
brain and the rest of the central nervous
system. The barrier stops potentially harmful toxins and pathogens
from entering brain tissue from the bloodstream.
To date, promising types of immunotherapy
that have passed clinical trials have not been very successful at crossing the
blood-brain barrier.
"Although our findings were not made in
humans," says senior study author Julia Y. Ljubimova, a professor of
neurosurgery and biomedical sciences at Cedars-Sinai Medical Center in Los
Angeles, CA, "they bring us closer to developing a treatment that might
effectively attack brain tumors with [systemic] drug administration."
Using drugs that can treat the brain
systemically — that is, by using the bloodstream to deliver them — would be an
advantage over treatments that only work when doctors inject them directly into
brain tissue.
The new study is also the first to describe
an immunotherapy that can stimulate immune systems both throughout the body and
local to the tumor in
mice.
An aggressive brain cancer
Although they only represent a small
percentage of cancer cases, brain cancers account for a disproportionate number
of deaths.
According to the National Cancer Institute,
which is one of the National Institutes of Health (NIH), an estimated 23,820 people in the United States will find out that
they have brain cancer in 2019, and 17,760 will die of the disease in this same
year.
These figures show that while brain cancer
will only account for 1.4% of cancer cases, it will be responsible for more
than double this percentage of cancer deaths (2.9%) in the U.S. in 2019.
Between 2009 and 2015, fewer than one-third of people with brain cancer in the
U.S. survived 5 years or more following diagnosis.
About 15% of primary brain tumors are
glioblastomas.
Glioblastomas are
particularly aggressive and fast growing because a large number of their cells
are replicating and dividing at any given time.
These tumors readily invade neighboring
regions of the brain.
Removing the shield against
immune attack
One of the features that make brain tumors
aggressive is their ability to suppress attack from anticancer cells in the
local immune system.
Prof. Ljubimova
explains that these tumors use immune cells, such as special macrophages and T
regulatory cells, as shields against anticancer cells.
So, she and her colleagues decided to pursue
a type of immunotherapy that uses checkpoint inhibitors to switch off the
macrophages and T regulatory cells and thereby activate the cancer-killing
cells.
They developed a nano-immunotherapy that can
carry checkpoint inhibitors across the blood-brain barrier. The transporter is
a small protein, or peptide, that attaches to the drug by means of a
biodegradable polymer.
Without the protection of their shielding
cells, the tumor cells are vulnerable to attack by lymphocytes and microglial
cells that can eliminate cancer cells.
"The checkpoint inhibitors can then
block the [T regulatory cells] and macrophages, allowing the local immune cells
to get activated and do their job — fight the tumor," Prof. Ljubimova
explains.
The new immunotherapy has to undergo further
tests before it is ready for human trials.
"We
hope that by delivering multifunctional new-generation drugs through the
blood-brain barrier, we can explore new therapies for many neurological
conditions.
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