Transcriber: Denise Scotti
Reviewer: David DeRuwe Everybody in this room has a loved one
who was diagnosed with cancer, who fought the disease
and experienced many side effects. Thanks to cutting-edge research, the understanding of the mechanisms
of disease, and availability of new drugs, now many cancer types
are largely curable. Not all cancer patients can benefit
from a curative treatment outcome. Last month, the singer of the band
The Wanted died at the age of 33, 17 months after he was diagnosed
with a tumor in his brain, leaving behind his wife
and two young children. I bet you can also recognize some
of these prominent people who also died prematurely from a very aggressive type
of brain cancer - glioblastoma: In fact, in the past four decades, we haven’t seen any improvement
in the survival of cancer patients, and 90% of them will not be alive
24 months after diagnosis. The current standard of care therapy
involves resection of the tumor, radiation, and systemic
administration of chemotherapy. And despite this aggressive
treatment regimen, the tumor will come back usually
ten months after initial resection and will remain largely incurable. This is an MRI scan of a patient
that was diagnosed with brain cancer. He was scheduled for surgery
to remove the tumor, and you can appreciate
that right after surgery, there are leftover cancer cells
that could not be removed, here in white. Those cancer cells camouflaged
themselves among healthy cells, making it really difficult
to discern and eliminate them. Despite chemotherapy and radiation,
the tumor continues to grow, it spreads locally, and then infiltrates
into other regions in the brain. So why can’t we eliminate
this brain cancer? Based on clinicians, the top three reasons
are delivery, delivery, and delivery. You see, when we treat
tumors in the brain, every drug therapy will have
to overcome one major obstacle on its way from the
bloodstream to the brain, and this is the blood-brain barrier,
a membrane that’s designed to protect the brain from invaders,
from viruses, and bacteria. What it means, though,
is that therapeutic molecules and antibodies that could have been
effective in diagnosis and therapy cannot penetrate
the blood-brain barrier either. So how can we actually target
brain cancer cells? Here we turn to Spider-Man for inspiration to see how
we can eliminate these supervillains. So Spider-Man used his superpowers
to cast a sticky web that would get him to the places that he needs that will halt
the supervillains in their tracks and eliminate them from escaping. What if I tell you that we can
use the same superpowers to eliminate brain cancer? We developed a sticky web
that contains drugs that you can see here
in this microscopic image in red that can be applied during surgery
to the tumor resection cavity. This material allows the drug
to be released locally, eliminating the need to cross
the blood-brain barrier, which means that we can use
any drug of interest. Here you can see how
we envision using the material: Following the resection
of the tumor in the brain, our material can be injected or sprayed. It’s composed of two polymeric solutions
that are based on FDA-approved materials. Because we deliver it locally, the drug can be released over time
and it will impart better efficacy. So now that we deliver the drugs locally, we can actually use very potent drugs
that could not be delivered otherwise because of systemic toxicity
when they’re delivered in the bloodstream or because of their inability
to cross the blood-brain barrier. So we tested the efficacy
of our sticky web when impregnated with a very potent drug
that we’ve identified using mouse models. Here you can see that when we induce
tumors in the brain of mice, in the absence of treatment, the tumor
will grow very rapidly within 12 days. What's shocking, though,
is when we deliver the clinically-used chemotherapy
drug temozolomide, the tumor continues to grow. When we deliver a very potent drug
using our technology, the tumor is eliminated. We’ve actually evaluated mice survival. And you can see that upon tumor induction,
in the absence of treatment, all the mice will die within 22 days. When we deliver the chemotherapy drug
that's now used in the clinic, we don’t see any benefit. Even when we deliver
the potent drug that we’ve identified, but we inject it directly
to the tumor in a free form, we don’t see benefit. This is because drugs are being cleared
and washed out very rapidly in the brain. When we deliver this potent
drug using our adhesive technology, you can see that now almost
60% of the mice are cured. And now when we can control the tumor and we combine it with their clinically
available chemotherapy, we can reach 80% curative
outcomes for the mice. Now, this was exciting. Brain tumors rarely metastasize
or spread outside the brain, but they do recur locally, so we wanted to evaluate whether the cured mice that we treated
can actually reject brain tumors. To do that, we re-challenged those mice. We’ve injected them with additional
cancer cells to grow the tumor and wanted to see what happens. The amazing thing
is that all these mice survived, in the absence of additional therapy. Their immune system was able to recognize
those cancer cells and eliminate them. Our therapy was acting as a vaccination,
eliminating the cancer cells, and also using them to educate
the immune system to identify them, such that these mice became protected in the future
from these invasive cancer cells. We are now testing the ability
of our technology to improve the efficacy
of new emerging immune therapies, and we already have generated
very promising results. So the advancement in our understanding
mechanisms associated with brain cancer and availability of new
and potent immunotherapy drugs can in principle result in better outcomes
for brain cancer patients. But the missing link is delivery systems, those that would allow the drugs
to enter the brain and reside in the brain for prolonged periods of time. After a decade of research,
a brilliant scientist in my lab, and through our collaboration
with the director of neurosurgery at Johns Hopkins University,
Dr. Henry Brem, together with Betty Tyler and their team,
we can now cure mice from brain cancer. I hope that what that means for patients is that we will be able to use biomaterial
superpowers to shuttle drugs, to wherever they need to be
for prolonged periods of time. This will enable eliminating
systemic side effects and using potent drugs that could
have not be used otherwise. As a biomedical engineer, my dream
is that one day we’ll be able to translate the technologies from the lab to patients
to save more lives than we currently can. Thank you. (Applause)
