>>Campbell Brown: It's an amazing story and
it's very serendipitous how you came up with
the idea of the HIV virus to potentially cure
cancer.
Talk about where it started, where the idea
came from.
>>Carl June: So Cameron, this is a field called
synthetic biology where most medicine is try
to restore and fix problems and not really
do -- you know, make things better than nature
could do.
So we have evolutionary biology, which is
how we got here, but I learned from athletics
and so on that, you know, steroids and drugs
could make your muscles better than nature
made them.
And now in medicine, we're trying to do the
same thing, which is in this case make the
immune system more potent.
So we've known for a long time that the immune
system responds to cancer, but it usually
loses, the immune system, and cancer wins.
So now we have approaches to make the immune
system better than it was born, and in my
case, it turned out to be I was forced into
the field of HIV research.
I was going to Stanford in 1971 and I got
drafted into the Navy because of the Vietnam
War, and in the Navy and in the military,
you're not allowed to do cancer research but
you are allowed to do infectious disease research.
So that's what I had to do until I got out
of the Navy.
>>Campbell Brown: So you were a cancer specialist
who was sort of forced into infectious disease
or --
>>Carl June: Yeah.
I was trained medically as a physician in
cancer but then I had to do 10 years and I
was glad I did it now because I had my feet
in two fields.
So this cross-cutting thing.
I learned how to engineer HIV.
And then when I got out of the Navy, I then
started to do what I always was trying to
do, was work on leukemia.
And so we -- you know, Emily was the first
child to ever be treated with an HIV-engineered
T-cell.
And our patient that we're going to have come
up here was the second man ever to be treated.
We first had to start treating adults before
we could treat kids, so we have a lot more
experience in the adults now.
>>Campbell Brown: So when you first thought
this could potentially work, was there kind
of an "aha" moment that got you to a place
where you said, "Okay, we should try this.
This is" --
>>Carl June: I mean, we made incremental -- you
know, I've worked on this for about 25 years.
We first had to learn how to grow T-cells.
So in the film it's not clear but the cells
were out of Emily's body for 10 days and that's
during the time when they're reprogrammed
to become leukemia-specific, we say, serial
killer cells, where in the movie it showed
each T-cell could kill a thousand tumor cells.
So that became the idea was to make the first
self-replicating drug.
So we give cells to the patient once and they
last the rest of their life, was the idea,
which we know from vaccines, that can happen.
If you have a good immunization as a child
you're protected the rest of your life.
And so we had a number of advances over the
years to solve the different problems in growing
the T-cells and engineering them, and then,
you know, we started our trial with trepidation
because it was the first time people had ever
-- cancer patients had ever had an HIV-engineered
cell.
And the first three patients had striking
results but they had what we call -- in oncology
and medicine, they had what's called on-target
toxicity.
So they had -- Emma had fevers of 106 degrees
for a week, and that was what medical oncologists
call -- is called shake and bake, but it was
not due to infection, it was due -- she had
pounds and pounds of tumor, and the patient
you're going to meet next had five pounds
of tumor that went away over a period of about
a week.
And that's a violent reaction that the immune
system does to get rid of this -- the tumors.
So we saw that in our first patient and we
didn't know what it was until the results
came back and we couldn't find leukemia anymore,
and so then we figured it was good.
[ Laughter ]
>>Carl June: And now when we treat patients,
they all start really having celebrations
when they get a 103-degree fever or more.
It's an amazing thing.
So on-target toxicity is okay.
The problem with previous oncology and cancer
therapies is the target -- the toxicity is
generally what's called off-target, so people
get nausea, vomiting, their hair falls out,
and the things you've seen with chemotherapy.
That's doing nothing to help get rid of your
tumor.
That's side effects.
So now the new thing in oncology and so on
that will cure cancer will be on-target effects
with precision therapies, and we have now
the science to do that.
So we're at a tipping point now where we're
going to see a major change in the way cancer
is treated.
>>Campbell Brown: So talk about the success
rate.
We're going to meet Doug in a minute who is
--
>>Carl June: Yeah.
>>Campbell Brown: -- who's a great success
story, but you started with adults before
you could try this with children, as you said,
but how -- how overall successful has it been
with adults and children?
>>Carl June: Yeah.
So we've learned a lot.
I mean, our first -- you know, we treated
three patients in six weeks and all three
had really striking results, so, you know,
very advanced chemotherapy-refractory leukemia,
and then we ran out of the virus to engineer
the cells and so we didn't know then if we
just got lucky.
I mean, the literature is filled with reports
where the first patient treated does well
on some new experimental therapy and then
it can never be replicated.
So now we know that it can be.
We've treated about 50 patients, and the -- and
the 20 children, the response rate like Emily's
is over 80% now in people who have really
a death sentence because they can't -- there
is no therapy standard.
So we now know it wasn't a fluke.
And then the other thing we know is that the
patients haven't relapsed.
So we've treated 30 patients like the patient
you'll see, Doug Olson, the adults with chronic
leukemia, and no one's relapsed.
So that's the power of the immune system is
it can be -- both have the killing effect
on the tumor and then it can have what's called
immunosurveillance but basically cells -- these
CAR cells hang around in a patient and now
are on surveillance for either recurrent tumor
or new tumor that might arise.
>>Campbell Brown: So you're talking about
a cure.
This isn't a treatment.
>>Carl June: So, you know, I stuttered when
that --
You know, that film, by the way, I want to
give a shout out to Ross Kaufman.
He was the producer of that film.
He did "Born in the Brothels," so he came
and made that three-minute documentary, and
I couldn't even say the word "cure" because
in cancer we never have done that.
We've had therapies that try to control the
disease or put you in remission, but it's
-- you know, so now I think with the targeted
therapies and the understanding, the goal
in cancer will be curing them.
And, you know, it's early on.
We have 50 patients.
We can't find a single leukemia cell in Emily
or in Dr. Olson, who you're going to meet
next.
But whether they're cured, you know, is going
to take a lot longer observation.
>>Campbell Brown: So where -- where are you
in the process?
So, you know, you've had extraordinary success,
but to the average person out there who reads
about your success, this is not available
to them?
>>Carl June: No.
And that -- you know, that keeps me awake
every night.
I have had thousands and thousands of emails
from people who want to be treated, and we've
treated 51 patients at the University of Pennsylvania
and it is not available anywhere else.
And so we're at an issue where we have a limiting
resource.
So it's, for instance, like organ transplantation
and how do you allocate those.
So we're dealing with that.
But fortunately, you know, we're in an area
where there's a been a valley of death.
There has been no pharmaceutical investment
in this kind of area.
It's all been done in the academic arena,
because there's very -- people tried these
things before and they didn't work.
There are very disappointing results.
So when we published our first three cases
back in 2011 and we had a lot of people knocking
at our doors, and I'm pleased now to say that
Novartis just a year ago, you know, invested
in this and they've made a large plant and
it's now become an engineering problem.
What we do now is it's a boutique way to grow
the patient's cells and it takes Ph.D.s to
do that, and so highly -- and there are not
enough Ph.D.s to treat, you know, common cancers.
Fortunately, you know, leukemia in children
is an orphan disease and the process we have
right now can be made available to everyone
by Novartis just by training enough technologists.
But to do a common cancer like breast cancer
or lung cancer, it needs to be automated and
that means robots.
So what the pharmaceutical industry can do
is now make CAR -- these are called CAR T-cells.
Chimeric antigen receptor T-cells.
But the analogy now is really to Detroit.
I mean, the initial assembly lines for automobiles
were all done by hand and they went along
and put cars together.
The kind of CAR T-cells that we have now need
to be done by robots and now robots assemble
80% of the cars in Detroit and so there's
just been no investment to date in this kind
of technology for, you know, cell-based therapies.
I think as the pharmaceutical industry, you
know, does this -- it's now an engineering
problem.
Not a scientific problem anymore, but engineering.
And now that that investment will be made,
we'll be able to extend this kind of approach
to diseases like HIV and AIDS and be able
to control those diseases with engineered
cells rather than having to take drugs every
day, and we'll be eventually able to treat
autoimmune diseases that -- you know, where
the immune system needs to be shut down rather
than turned on, like we do for cancer.
So I think, you know, there will be a new
industry to do this.
>>Campbell Brown: So the next steps, FDA approval
and -- is there a time line?
You know, what is -- give people some sense
of what it might be like.
>>Carl June: Well, so it's, you know, the
usual time line, which is embarrassing, but
from when you first treat a patient, you know,
the beginning trial -- it's called a Phase
1 trial -- that average time is 12 years to
when it gets commercially approved.
>>Campbell Brown: Wow.
>>Carl June: And, you know, we -- and it costs
about $600 million per drug.
That's what we face these days and it's very
inefficient.
And here we have this so-called valley of
death where we did a lot of -- everything
was done in the academic sphere but there
was no investment in having the commercial
launch.
You know, making the industrial plants, the
industrial scale.
It was all in our little boutique place at
the university.
So now there's this catch-up time that the
industry is doing.
But they actually think, because the results
are so striking, that it can be, you know,
commercialized on the results from small numbers
of patients on trials, and that maybe in three
or four years this will be, you know, available
worldwide.
[ Applause ]
>>Campbell Brown: So let me bring up Doug
Olson.
Doug, come on up and join us.
[ Applause ]
>>Campbell Brown: Doug is a survivor.
[ Applause ]
>>Campbell Brown: So 
he is one of your success stories.
Doug, tell people what kind of shape you were
in when this was presented to you as a possible
option.
>>Doug Olson: Well, actually the study -- the
story started back in 1996 when I was diagnosed
with cancer, CLL for chronic lymphocytic leukemia
to be exact.
Needless to say, I was terrified.
I was only 49 years old.
I had a wife and four kids.
My daughter was only 9 years old and, you
know, I just couldn't bear the thought of
her growing up without me.
But I was really lucky.
I didn't have to be treated for a while.
And then it was just mild treatment for years.
But by 2010, my disease had progressed to
the point where it was now resistant to standard
chemotherapy and over 40% of my bone marrow
was now cancer cells.
>>Campbell Brown: It was bone marrow transplant
or -- I mean, that was your last --
>>Doug Olson: David Porter, my oncologist,
sat me down and he said it is time to think
about a bone marrow transplant but it is still
pretty risky and only about 50% cure rate.
That really was the only choice I had.
Otherwise, it was about -- he said it was
probably about two years.
>>Campbell Brown: And then he said, There
is this one clinical trial.
>>Doug Olson: And then about a month later
he said, We have this new trial where we can
take your white cells and use them to kill
the cancer.
So my wife and I read the protocol, and it
looked like it ought to work.
So I was in, absolutely in.
They talk about cancer as a battle, and I
will tell you it is.
That's one of the reasons I wanted to do this
was because it was really an opportunity to
fight back, you know, so that you are not
just a victim of your disease.
>>Campbell Brown: And it was -- I mean, you
got sick.
It is everything that the doctor described,
the fever and -- you were really sick, right,
as the treatment started?
>>Doug Olson: They transformed my white cells
and then started to over three days infuse
them.
Nothing happened.
It was rather anticlimactic for about a week,
actually two weeks.
And almost to the hour, I woke up with a fever
and chills and that's when I knew it was working.
>>Campbell Brown: You were happy.
It's working!
>>Doug Olson: Strangely enough, yes.
I was pretty excited that something was happening.
So it was about a week -- a little over a
week, the symptoms persisted.
It's like having the flu only much worse.
Got to the point where I had to be hospitalized
because my kidneys were getting in trouble.
But, literally, I think, overnight when they
treated the symptoms, I started feeling better.
I think it was that day or the next David
Porter walked into my hospital room and he
is holding his cell phone and he said, "Hot
off the press.
18% of your white cells are CART19 cells."
He said, "Doug, we can't find a cancer cell
in your body.
Your bone marrow is completely clean."
>>Campbell Brown: Completely.
>>Doug Olson: And you can imagine, I decided
at that point to declare victory, I was going
to be okay.
So...
[ Applause ]
>>Campbell Brown: I think we have a picture.
Let's put up the picture, if we do, of what
you did when you found out you were cancer-free.
He is on a sailboat.
>>Doug Olson: So I was discharged from the
hospital on that Friday.
My wife picked me up from the hospital.
We drove straight to the Indianapolis boat
show and bought a sailboat.
I mean, think about it.
Just a few weeks before I wasn't so sure I
had a future.
And overnight everything changed.
There was a future, and it was pretty amazing.
>>Campbell Brown: And he's remained cancer-free?
There's been nothing?
>>Carl June: Just had his third-year anniversary
from the treatment.
And two things we found.
I mean, the bone marrow -- we can analyze
down to one in a million cells and find leukemia
cells.
So we know to that level there are none.
We can't obviously analyze his whole body.
So only time will tell.
But he has no leukemia that we can find.
And he still has these CART cells so they
are there in the surveillance mode.
So we now know that they can last for at least
three years and that's really great news.
[ Applause ]
>>Campbell Brown: So I guess how confident
are you?
We don't know yet because it is not enough
time has passed that this will, you know,
be a stable outcome?
>>Carl June: That's the -- Novartis now will
start next year multi-center international
trials.
So it will be the first time that a gene therapy
trial like this with cells complicated engineering
will become multi- -- they have always been
at single center boutique trials.
So it will become multi-center and international.
So that's a big step forward, I think, for
cancer therapies.
And, you know, our big thing next is to -- you
know, the whole field now will be asking,
Can this go beyond blood cancers?
I mean, right now it looks like most of the
cancers we now treat with bone marrow transplantation,
we can, if we are successful, get rid of the
need to have a bone marrow transplantation
and treat it with a patient's own cells.
So then the big thing next really is solid
cancers and can we do --
>>Campbell Brown: That's a big jump, right?
>>Carl June: Yeah.
They are much more common and, you know, generally
not curable.
Things like pancreatic cancer and brain cancer,
the therapy is the same as when I was a medical
student 30 years ago.
It is the same thing, and it doesn't work
unless you are really lucky and it's caught
very early.
So that's where we're going to put a lot of
our energies, is now moving over to the solid
cancers.
>>Campbell Brown: How optimistic are you given
the strike-through?
Has it sort of -- I mean, as you said, it's
-- it has been literally decades since there
has been a breakthrough like this in cancer
research.
Fair to say?
>>Carl June: Yes.
And I think, you know -- so there has been
lots of disappointments.
I think now the science advanced, and we can
see why the previous attempts failed.
And then now we have all the tools there to
both understand at a deep level the molecular
causes of cancer and then hit it where the
Achilles heel is.
We can design therapies now that will fix
it.
So I think the whole field in oncology is
very much energized now that targeted therapies
like this will replace the -- literally the
therapies that -- the most recently approved
therapy for chronic lymphocytic leukemia is
called Bendamustine and it is an analog of
nitrogen mustard, which is what was used to
gas people in World War II -- in World War
I actually.
It is nitrogen mustard.
It just breaks up DNA.
It is completely non-specific.
And that's what we used in the 1950s as the
first chemotherapy.
Hopefully -- it does cure some people, but
it is horribly toxic.
And there is a lot of optimism now that we
will move to a whole new paradigm of cancer
therapy.
>>Campbell Brown: It's amazing.
Congratulations to you, Dr. June.
As I said, it is an honor to be on the stage
with you.
And, Doug, congratulations to you, too.
Thank you so much.
>>Doug Olson: Thank you.
[ Applause ]
