Virus bunuh sel kanser
Poliovirus kills off cancer cells, stops
tumor regrowth
Researchers from Duke University in
Durham, NC, may have discovered a new way of killing off cancer cells.
The team was jointly led by Dr. Matthias Gromeier, a professor
in the Department of Neurosurgery, and Prof. Smita Nair, who is an immunologist
in the Department of Surgery.
The new research -
which is published in the journal Science
Translational Medicine - shows how a modified poliovirus
enables the body to use its own resources to fight off cancer. The
modified virus bears the name of recombinant oncolytic poliovirus (PVS-RIPO).
PVS-RIPO has been in clinical trials since
2011 and preliminary results have offered hope to patients with one of the most
aggressive forms of brain tumor: recurrent glioblastoma. So,
the researchers set out to investigate more deeply how exactly PVS-RIPO
works.
Explaining the rationale behind their research endeavor, Dr.
Gromeier says, "Knowing the steps that occur to generate an immune
response will enable us to rationally decide whether and what other therapies
make sense in combination with poliovirus to improve patient survival."
Poliovirus attacks tumors,
inhibits regrowth
The researchers examined the behavior of the poliovirus in two
human cell lines: melanoma and triple-negative breast cancer. They
observed that the poliovirus attaches itself to cancerous cells. These cells
have an excess of the CD155 protein, which acts as a receptor for the
poliovirus.
Then, the poliovirus starts to attack the malignant cells,
triggering the release of antigens from the tumor. Antigens are
toxic substances that the body does not recognize, therefore setting off an
immune attack against them.
So, when the tumor cells release antigens, this alerts the
body's immune system to start attacking. At the same time, the poliovirus
infects the dendritic cells and macrophages.
Dendritic cells are
cells whose role it is to process antigens and "present" them to T
cells, which are a type of immune cell. Macrophages are
another type of immune cell - namely, large white blood cells whose main
role is to rid our bodies of debris and toxic substances.
The cell culture results - which the researchers then verified
in mouse models - showed that once PVS-RIPO infects the dendritic cells, these
cells "tell" T cells to start the immune attack.
Once started, this process seems to be continuously successful.
The cancer cells continue to be vulnerable to the immune system's attack over a
longer period of time, which appears to stop the tumor from regrowing.
As Prof. Nair explains, "Not only is poliovirus
killing tumor cells, it is also infecting the antigen-presenting cells, which
allows them to function in such a way that they can now raise a T cell response
that can recognize and infiltrate a tumor."
"This is
an encouraging finding, because it means the poliovirus stimulates an innate
inflammatory response."
Prof.
Smita Nair
Speaking to Medical
News Today about the clinical implications of the findings and
the scientists' directions for future research, Dr. Gromeier said, "Our
findings provide clear rationales for moving forward with clinical trials in
breast cancer, prostate
cancer, and malignant melanoma."
"This includes novel combination treatments that we will
pursue," he added.
More specifically, he explains, because the study revealed that
after treatment with the poliovirus "immune checkpoints are increased on
immune cells," a future strategy the researchers plan to explore is
"[oncolytic] poliovirus combined with immune checkpoint blockade."
.
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