Translator: Tanya Cushman Reviewer: Peter van de Ven
I'm a professor, so I feel obliged - I wouldn't be earning my keep -
if I didn't share a few facts right off the top,
and the facts that I want to share with you
is that every three minutes a child is diagnosed with cancer.
That means every 24 hours
enough children to fill St Mark's School are diagnosed with cancer,
and consequently, cancer in children
is the leading disease contributor to childhood mortality in our country.
Cancer in children.
Equally as shocking to me is that we still, in the cancer clinic,
rely on fairly antiquated therapies:
radiation therapy and chemotherapy.
These are therapies that are not smart enough to go into a child's body,
eliminate the cancer cells
and leave their growing, maturing body unharmed.
They take their toll.
Indeed, as a pediatric oncologist,
it's really heart-rending to know that while we might take a child with cancer
and give them a remission, potentially a cure,
we take a child with cancer,
and we create the chronically ill young adult of tomorrow.
Children deserve much better than this,
and even with our best therapies,
there's a lot of pediatric cancers we see in the clinic that we can't cure.
So I know this collective community of doctors and scientists
have a vision of a different future
for caring for children with cancer and adults as well.
We believe our work will not be done
until every child has a cure waiting for them at the time of their diagnosis,
and the therapy is good enough, smart enough, precise enough
that we can cure cancer without harming the body along the way.
So, how might we be able to do this?
And this is where we're going to get nerdy:
we're going to talk about molecular biology,
genetic engineering, protein use -
don't worry, take a deep breath; it's going to be okay.
What if the power to cure cancer
is already in our body; it's part of our body?
What if it's our immune system?
I was tantalized with that thought many, many years ago,
and I took plan A.
I wanted to try to be a physician scientist,
learn from my patients in the clinic,
go back to the laboratory and create solutions for them.
No one pointed out that that might be a 20-year journey
until you started seeing the fruits of your labor,
and, indeed, we have a saying in research
that if we knew what we were doing it wouldn't be called research;
that's the path.
So, what about our immune system?
It's this incredible part of our body
that protects us every day from the common cold.
If a friend a sneezed on you on your way into the auditorium,
you may have a runny nose and some aches and pains
while you have a fever for a couple days,
and then your body heals itself - it gets rid of that invading virus.
Can we turn the immune system against cancer?
And if we did,
would being cured of cancer
feel no worse than you have a cold for a couple days?
That's the possibility.
So in our laboratories,
we focus on white blood cells of the immune system.
I will say the T-cell is probably the Maserati of the immune system;
I'm biased.
But this is what T-cells do every day for us;
they are running around our body protecting us from invaders like viruses.
You see the small cell there?
That's the T-cell. It has sensors on it.
It can detect if a cell has a virus hiding on the inside.
And when it does,
an alarm system goes off in that T-cell;
it drills holes in the membrane of that virally infected cell;
puts little proteins inside that make that cell die
and digest all the virus along the way.
This is how our immune system works every day.
So what about cancer?
What about patients with cancer?
They have good T-cells.
What we're learning is that cancer works very hard in our bodies
to become invisible to the immune system,
to create a false sense of peaceful co-existence
when we really want a battle to take place.
How can we overcome that?
So we started thinking about T-cells like you would your smartphone.
You may need an app to find the nearest Starbucks
to find that cup of coffee.
T-cells need an app to be able to bump up against a cancer cell
and do exactly what you just saw
when it bumped up against a virally infected cell.
So what do we do?
We take our research, and we think,
"Well, T-cells need apps."
They're not going to be apps that are coded in computer code;
they're going to be coded in recombinant DNA code.
And we started making apps now
that create something that comes to the surface of the T-cell
that wasn't there before,
and you can think of that as an artificial Velcro-like molecule,
a lock-and-key,
that now, when the T-cell bumps up against a cancer cell,
there's a lock-and-key fit,
very specific and precise,
and it triggers the T-cell to do something it couldn't before:
to kill a cancer cell.
What would it mean if we can develop this technology
and make it a therapy for patients in the clinic?
It would mean that when you had a diagnosis of cancer,
a tube of blood would be taken by your doctor;
it'd be shipped to a T-cell factory,
and a week later, your T-cells would come back to you -
cells from your own body now equipped to get rid of the cancer in your body,
ideally with minimal side effects.
So, I want to show you the next step
when we started seeing results that really got us excited.
What you're going to see is a Petri dish
that's full of very aggressive pediatric cancer called neuroblastoma,
and the little cells that we add in
are the reprogrammed T-cells with the Velcro molecule we've designed.
Here come the T-cells;
now, my kids call these like the Pac-Man cells.
I don't have to say much;
as you see what's going on in this Petri dish.
These T-cells are making that attachment,
and they're sending their alarm system signals
to kill those cancer cells.
You might notice there's one cancer cell up on the screen there.
Will that be the one that survives and causes a relapse?
And the answer is no.
Now the Petri dish is just full of T-cells that want to see more cancer cells
and do it over and over again.
It's a living therapy that would get stronger in your body
as long as there were any cancer left,
and then they could stay in your body for prolonged periods of time.
This is a very different medicine that we think about in the hospital.
So, this is the best part of the story:
I want to introduce you to Greta, a beautiful, beautiful baby,
who, at about eight months of age,
became listless, pale, started having fevers and easy bruising.
And Greta was diagnosed with acute lymphoblastic leukemia,
a very aggressive form of leukemia when it affects babies.
Her parents took her to Seattle Children's Hospital;
she had state-of-the-art chemotherapy - almost a year of chemotherapy -
and the leukemia came back.
She had a bone marrow transplant,
that almost took her life from the side effects of that treatment,
and the leukemia came back.
And, in fact, when our first FDA trial for pediatric leukemia
with the reprogrammed T-cells
was approved by the FDA,
Greta's parents were actually having to deal with the possibility
that they would take her home for hospice
to keep her comfortable for the next days or weeks of her life.
And her parents heard about a different kind of therapy,
T-cell immunotherapy,
and they wanted to try.
So when we first met Greta, we did a bone marrow test.
What's important about this test
is all the cells should be blue in the bone marrow;
there shouldn't be any red cells - those are the cancer cells.
You can see more cancer cells in her bone marrow than normal cells;
she had very aggressive leukemia.
So we took a tube of her blood; it went into our T-cell factory that we built,
and we made her reprogrammed T-cells.
The whole dose of T-cells
that we were going to treat for about a pound of leukemia in her body
is that little white clump of cells in that test tube -
about a baby aspirin worth of T-cells.
And you can see Greta when she received her treatment,
a single dose taking about three minutes without any side effects.
Greta would have told us if there were side effects.
So she entered the trial; her T-cells were ready.
They went back to the hospital clinic where she and her parents were waiting.
She received the infusion, and it was wonderfully boring:
nothing happened; it was without side effects.
And then we watched Greta,
and interestingly, for a couple days she had flu-like symptoms and fever.
We didn't know what could be the cause.
Was it good? Was it bad?
So, you can imagine,
three weeks after her T-cells,
we all held our breath as we did a repeat bone marrow exam.
And imagine everyone's joy
when there wasn't a single luekemic cell in her sample;
she was in complete remission.
Well, Greta now gets to come back and visit us.
Here she is; she's growing up.
She continues to be in remission.
We've had an over 90% success rate with terminally ill children with leukemia,
with this reprogrammed T-cell therapy.
I wonder a lot about what Greta will be.
Will she be the star pitcher of her Little League team?
Will she be a Saint Marker?
Will she be a poet? a scientist? an engineer?
The beauty is we now get to find out;
she's with us.
So, with closing, I hope this was a story of our endeavor,
our society's endeavor,
to overcome this problem of cancer in children.
I really hope at some point I get the privilege to write
in a medical history book
that there was a time in medicine
where we actually tried to help patients
by giving them poisonous medicine and radiation,
and how the grip of childhood cancer
was released through novel immunotherapies.
Thank you.
(Applause)