>>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 ]