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)