Lawan kanser dengan Virus Polio
Poliovirus Therapy Induces Immune Responses
Against Cancer
Investigational
therapy directly kills tumor cells and unmasks them to the body’s defenses
DURHAM,
N.C. – An investigational therapy using modified poliovirus to attack cancer
tumors appears to unleash the body’s own capacity to fight malignancies by
activating an inflammation process that counter’s the ability of cancer cells
to evade the immune system.
Describing
this process in a paper published Sept. 20 in the journal
Science Translational Medicine, Duke Cancer
Institute researchers provide the first published insight into
the workings of a therapy that has shown promise in early clinical trials in
patients with recurrent glioblastoma, a lethal form of brain cancer. The
modified poliovirus received a breakthrough therapy designation from the Food
and Drug Administration last year, expediting research.
“We
have had a general understanding of how the modified poliovirus works, but not
the mechanistic details at this level,” said co-senior author Matthias Gromeier, M.D., a professor in the
Duke Department of Neurosurgery who developed the therapy. “This is hugely
important to us. 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.”
Gromeier,
with expertise in cancer biology, collaborated with fellow Duke researcher and
co-senior author Smita Nair, Ph.D., an immunologist and
professor in the Department of Surgery. The research team elucidated how the
poliovirus works not only to attack cancer cells directly, but also to trigger
a longer-lasting immune response that appears to inhibit regrowth of the tumor.
Using
human melanoma and breast cancer cell lines, and then validating the findings
in mouse models, the researchers found that the modified poliovirus therapy
starts by attaching to malignant cells, which have an abundance of CD155
protein. The CD155 protein is otherwise known as the poliovirus receptor. The
modified virus then begins to attack the tumor cells, directly killing many,
but not all. This releases tumor antigens.
The
second phase of assault is more complicated. By killing the cancer cells, the
modified poliovirus triggers an alarm within the immune system, alerting the
body’s defenses to go on the attack.
This
appears to occur when the modified poliovirus infects dendritic cells and
macrophages. Dendritic cells then present tumor to T cells to launch an immune
response. Once the immune system is activated against the poliovirus-infected
tumor, the cancer cells can no longer hide and they remain vulnerable to
ongoing immune attack.
“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,”
Nair said. “This is an encouraging finding, because it means the poliovirus
stimulates an innate inflammatory response.”
Nair
and Gromeier said further studies will focus on the additional immune activity
following exposure to the modified virus.
In
addition to Gromeier and Nair, study authors include Michael C. Brown, Eda K.
Holl, David Boczkowski, Elena Dobrikova, Mubeen Mosaheb, Vidya Chandramohan and
Darell D. Bigner.
The
study received support the Public Health Services (CA197264, CA124756 and
CA190991), the Department of Defense, (W81XWH-16-1-0354); the Lefkofsky Family
Foundation, Hope & Gavin Wolfe, and the BLAST Glioblastoma Foundation.
Nair
and Gromeier, along with Brown, Chandramohan and Bigner, own intellectual
property related to this research, which has been licensed to a company, Istari
Oncology, Inc. Gromeier and Bigner are cofounders and equity holders in the
company.
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Cancer
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