Virus Polio Rawat barah otak
The idea that viruses may be co-opted to do
good rather than harm isn’t entirely new; researchers have been attempting to
harness the power of viruses and bacteria for more than a century. Vaccinesare the shining example of using bad
bugs to do good in priming the immune system to fight disease.
But disease-causing viruses aren’t always
easy to corral, and attempts to use them to activate the immune system against
things other than fellow bacteria and viruses — including cancer, for example —
have not been so successful. There is only one approved virus-based treatment
for cancer, which uses herpes virus against melanoma.
In a new report published
in the New England
Journal of Medicine, however, scientists led by a team at Duke
University report they may have trained another virus to target cancer, by
using poliovirus to target brain tumors.
Dr. Darell Bigner,
emeritus director of the Preston Robert Tisch Brain Tumor Center at Duke
University Cancer Center, and his team engineered a poliovirus that was designed to target a difficult-to-treat
brain cancer known as glioblastoma. Among a group of 61 people who had
failed to respond to current therapies, which include radiation and
chemotherapy, 21% who received the poliovirus treatment were alive after three
years, compared to 4% who generally survive that long following standard
therapy.
The virus-based therapy is
the culmination of 20 years of work by Bigner’s colleague Dr. Matthias
Gromeier, professor of neurosurgery at Duke, who engineered a poliovirus that
could activate the immune system but not cause polio. He accomplished that by
swapping out one of the poliovirus’ genes for a similar one found in the
rhinovirus that causes the common cold. Poliovirus has evolved to become quite
adept at infecting certain human cells, by targeting a molecular door on these
cells known as CD155. This door, or receptor, is found on cells in the
intestines, and in motor nerves in the spinal cord, which explains why
poliovirus infection causes paralysis. (Poliovirus that infects intestinal,
cells, however, often doesn’t cause serious health problems or even many
noticeable symptoms.) It is also found on many solid tumors as well, including
glioblastoma.
When Gromeier’s modified poliovirus
infected these brain cancer cells, it began to kill some of them. But more
importantly, the virus also recruited other immune system cells to launch an
attack on the cancer cells. The poliovirus made these additional immune cells
“extremely angry,” says Gromeier, which is a good thing for fighting the cancer
— but only to a certain extent. An over-activated immune response can cause
serious inflammation, and the researchers had to lower the initial dose of the
virus therapy, which they injected directly into the tumors in the brain,
several times before they found the right balance for an immune attack on the
cancer.
As aggressive as that initial immune
assault can be, however, it can dissipate just as quickly, when the virus
starts to die off. Poliovirus is designed to infect cells and reproduce for a
few weeks, and once the microbes have done their work in infecting cells, their
anti-cancer effect wanes as well. But Bigner and his team are optimistic that
they can address that potential shortcoming by taking advantage of other recent
advances in immune-based therapies for cancer. They plan on combining their
poliovirus treatment with so-called checkpoint inhibitors, which release the
immune system to attack tumor cells with more abandon. (Normally the immune
system is trained not to attack cancer cells, since they are not foreign
intruders like bacteria or viruses, but the body’s own cells that grow out of
control.) “It’s a very obvious combination strategy for us that we will
pursue,” says Gromeier.
So far, Bigner says that eight of the 61
patients are what he considers long-term responders, who have survived longer
on the virus-based therapy than they would have if they had received radiation
and chemotherapy. Some of their tumors began growing again, but they were
treated with another dose of the poliovirus therapy, and were able to stop the
cancer from growing. Some were also treated with chemotherapy when the tumors
began to grow again, and “many of them responded dramatically; their tumors
fell apart,” says Bigner. His group is now conducting another trial to compare
people who are treated with the poliovirus therapy alone, or with the poliovirus
and a single dose of chemotherapy.
The people in the current study had all
been treated with standard therapies and saw their cancer return, but Bigner
hopes that the results lead to moving the virus-based immune therapy earlier in
the disease, when people’s immune systems are stronger and better able to
launch an effective attack against cancer. He is also encouraged that the
strategy will work against other cancers as well, and plans to start studies
with people diagnosed with melanoma and difficult-to-treat triple negative
breast cancer. Animal studies hint that the virus could be used against
pancreatic, prostate and stomach cancers, too.
“I’ve been doing this for 50 years and have
never seen responses in a study like this,” says Bigner. “The results, in terms
of long-term survival, are better than anything in the literature. And I think
we can build on this.”
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