An experimental program at Duke University is using a surprising new
weapon in the war on cancer — infusions of the polio virus that have
successfully been used to treat patients with inoperable brain
tumors.
While the doctors and researchers spearheading the effort are
reluctant to use the words “cancer cure” to describe the work, the
early success of the innovative effort is at least the next best
thing. If ongoing clinical trials of the technique continue to prove
promising, it could add a new way to treat cancer — alongside
surgery, radiation, and chemotherapy.
“The idea of targeting cancer with viruses has been around for at
least 100 years,” notes Matthias Gromeier, M.D., one of the lead
investigators heading up the new anti-cancer research at the Preston
Robert Tisch Brain Tumor Center at Duke.
“However, valid strategies of using ‘oncolytic’ (cancer-fighting)
viruses emerged only recently. This is mostly due to technological
advances in genetic engineering of viruses.”
The Duke project, which gained wide attention from a “60 Minutes”
report on Sunday, involves injecting a genetically engineered
poliovirus — known as PVS-RIPO — into deadly brain tumors. Early
testing involving primates and human patients has found PVS-RIPO
homes in on cancer cells and destroys them, without harming healthy
tissues.
Dr. Gromeier explains that the Duke team essentially disarmed the
virus through genetic manipulation, so it cannot cause polio, while
maintaining its ability to infect, target, and kill certain cells —
specifically brain tumor cells.
“To work against cancers in patients, oncolytic viruses must target
cancer cells for infection and they must kill them. At the same
time, they must be safe,” notes Dr. Gromeier, a professor of
neurosurgery, molecular genetics, and microbiology at Duke, who has
been working on the polio-virus project for 25 years.
“Accomplishing this is very difficult scientifically and only very
few viruses are suitable as cancer-fighting agents in the clinic. We
achieved this feat by genetic engineering to remove poliovirus’
inherent disease-causing ability.”
Dr. Gromeier explains that the resulting PVS-RIPO virus “naturally
infects [and] kills cancer cells, but not normal cells, because its
ability to grow (and kill) depends on biochemical abnormalities only
present in cancer cells.”
He adds that tests in patients have proven that PVS-RIPO has “no
ability to cause poliomyelitis, and no ability of to change back to
wild type poliovirus that can cause poliomyelitis.”
The treatment targets a form of brain cancer called glioblastoma,
which is what killed Sen. Ted Kennedy in 2009. It is a particularly
virulent cancer, killing about 12,000 Americans every year — 60
percent of whom die within two years of diagnosis, according to the
American Brain Tumor Association.
PVS-RIPO works by not only infecting and killing brain tumor cells
directly, but it also recruits the patients’ own immune response
against the cancer, Dr. Gromeier explains.
Once brain tumors are infected with PVS-RIPO, a patient’s immune
system recognizes and targets the virus infections and kills the
cancer cells. Just how PVS-RIPO harnesses the power of the body’s
own defenses to attack tumors that were infused with the virus is a
major research goal of Dr. Gromeier’s laboratory.
The research is still in early stages — so far undergoing what’s
known as a “phase one” clinical trial of the technique in cancer
patients with glioblastoma. Since 2012, at least five patients have
been treated, according to Duke.
One of the first patients in the trial died six months following
PVS-RIPO infusion, due to tumor regrowth. But none of the others
have had any toxic side effects — indicating PVS-RIPO is safe.
What's more, four are still alive, and at least two are cancer-free
three years after receiving the infusion of polio virus, the
researchers said.
Now, they are planning additional Food and Drug
Administration-approved phase two and phase three studies with
larger groups of cancer patients, including adults and children. If
they prove as promising as the first two cases, the approach could
lead to wider use of cancer-fighting viral agents in brain cancer.
Dr. Gromeier believes the approach holds promise against other forms
of cancer, as well.
“Because PVS-RIPO naturally targets and destroys cancer cells from
most common cancer types (pancreas, prostate, lung, colon, and many
others), it can be directed against these cancers as well,” Dr.
Gromeier says. “To establish this in the clinic, we plan future
clinical trials in patients with cancers other than brain tumors.”
If those follow-up studies prove successful, the FDA could give the
approach a so-called “breakthrough status” to fast-track its
development.
Duke isn’t the first or only research institution investigating the
use of viruses to kill cancer. More than 100 years ago, physicians
first reported unexpected cancer remissions in patients who came
down with the flu and, by the 1950s, scientific research into the
idea began in earnest.
New genetic engineering techniques developed in just the last two
decades have allowed scientists to modify viruses to target cancer.
Nearly a dozen biotech companies and research institutions are
experimenting with genetically engineered viruses to target cancer.
Biotech giant Amgen has been working on a herpes virus-based
treatment (called T-VEC) for melanoma. And several smaller companies
— including Oncolytics Biotech DNATrix and Oncos Therapeutics — are
reportedly conducting their own research.