FOR PATIENTS, SURVIVORS AND FRIENDS
Learn about cancer while you walk, drive or do
the dishes by listening to the Yale Cancer Center
Answers podcast, a weekly show featuring two
oncologists talking about screening, treatment,
prevention and other cancer-related topics.
Track symptoms and side effects with
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both where your pain is and its intensity. It
also allows you to see how your pain changes,
which can help your doctor treat your pain
If you have glioblastoma, consider participating in OurBrainBank, an app created to collect
patient data that may help researchers develop
new treatments. App users may choose to receive
information about clinical trials.
Q: How does the engineered virus
you are studying work?
A: The therapy we developed is
called Delta 24-RGD. We called it
that because we deleted 24 base
pairs from a critical gene in the virus
called E1A, which interacts with
retinoblastoma protein, a tumor
suppressor. When the virus gets
into a normal cell, it can’t replicate
because those cells have retinoblastoma protein. In tumor cells, the retinoblastoma protein is dysfunctional,
so when the engineered virus gets
in, it starts replicating like crazy. It
takes over the cancer cell and uses its
machinery to make more of the virus,
which moves through the tumor and
infects other cancer cells.
Q: How did you conduct the study?
A: One arm of the trial had 12 patients
who were going to have brain surgery
to remove the tumor. To deliver the
treatment, we drill a hole in the skull,
put a catheter into the tumor, and
then inject the virus. We waited two
weeks and then took out the tumor
so we could see what the virus did.
In those patients, we saw a large
number of immune cells in the tumor.
That was evidence that the virus
replicated and attracted immune cells
to the tumor.
There was another arm of the trial
in which we injected the virus into the
tumor but didn’t remove [the tumor].
In these patients, the tumor would
initially get worse but then start to go
away. In three of the 25 patients, the
tumor disappeared and stayed gone
for over three years, which is unusual
for brain tumors.
Q: Why do you think it worked so well
in those three patients?
A: That is the critical question and
the focus of our subsequent research.
I think it has something to do with
their immune system and its ability
to respond to the tumor. But it could
also be something about their tumor.
Q: What are the next steps?
A: There are a couple of pathways we
can take. We are looking at whether
using stem cells to deliver the virus
through the bloodstream will work.
We also think that the tumor is
making checkpoints that inhibit the
immune system, even after the virus
gets in. So, we’re looking at treating it
by injecting the virus into the tumor
and giving the checkpoint inhibitor
Keytruda (pembrolizumab) intravenously. We are also thinking about
giving the checkpoint inhibitor more
This is all experimental. There
have been no new treatments that
have significantly increased survival
for patients with glioblastoma for
20 to 30 years. This is a difficult
disease to treat, and we have no
misconceptions that this will be a
panacea. I think there is a subset of
people who will respond to this type
of therapy, and we will need to see
if we can find a biomarker to predict
who they are. —SUE ROCHMAN
Study Shows How Metastatic Tumor Microenvironment Changes
Using biopsies of high-grade serous ovarian cancer metastases, researchers were able to show how the cells and the proteins that
surround the tumor—its microenvironment—change as metastases develop and progress. In addition, the researchers identified 22
genes in the microenvironment associated with shorter overall survival in ovarian and 12 other cancers. According to the researchers,
their findings suggest it may be possible to develop drugs that treat cancer by altering the tumor microenvironment.
LEARN MORE IN THE MARCH 2018 CANCER DISCOVERY.