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)
