
Has Carl June Found a Key to Fighting Cancer? - gmatty
http://www.phillymag.com/articles/carl-june-key-fighting-cancer/
======
swombat
I really hope this is not another one of those false cures. It's time we made
some real big-news progress against this horrible collection of ailments we
call cancer.

For those who don't want to read through the lengthy human interest story
wrapping the news here, from a quick read I gathered they're basically
modifying T-Cells:

> _In their natural state, T cells usually aren’t able to kill tumor cells,
> partly because they can’t latch on strongly enough. But June was fascinated
> by scientific papers showing it was possible to change this. A few
> researchers—first an Israeli named Zelig Eshhar in the ’80s, then other
> investigators around the world—had discovered that you could force a T cell
> to stick to a tumor cell and kill it. To pull this off, you built an
> “engineered T cell”—a T cell never before seen in nature. You altered the T
> cell’s genetic blueprint by injecting a new gene into the cell. The new gene
> would tell it to build a new molecular limb. The limb, called a “chimeric
> antigen receptor,” would sit partly inside the cell and partly outside, and
> it could send signals either in or out. One signal it could send was: kill.
> Another was: replicate._

> _June loved this approach. So elegant. Put the immune system on steroids.
> What if you could train the body to fight cancer on its own? What if,
> instead of replacing a patient’s immune system (as in a bone-marrow
> transplant) or pumping him full of poison (chemo), you could just borrow
> some cells, tweak them, and infuse them back into the patient? In theory,
> the engineered cells would stay alive in the blood, replenishing themselves,
> killing any tumors that recurred. It occurred to June that one infusion
> could last a lifetime._

It seems this research has been going on for 10+ years. How many people have
died because of the glacial regulatory pace of cancer research?

~~~
grey-area
_I really hope this is not another one of those false cures._

 _It seems this research has been going on for 10+ years. How many people have
died because of the glacial regulatory pace of cancer research?_

One of these statements explains the other - verifying research is safe with
trials takes time, it's not something that should be rushed.

~~~
nazgulnarsil
Blanket statements like this aren't true. With a lethal ailment, a risk
analysis must be done on how many you are killing with each delay.

~~~
arkades
The vast majority of new treatments fail in Phase 2 - that is, in showing
effectiveness in a human model. A huge chunk of the remainder fail in phase 3.

People whine about how slow the pace of research is, but that's not because
clinical trials are so slow - it's because most drugs _fail_. The vast
majority of drugs that work in animal models get bounced in Phase 1 (when they
show unacceptable toxicity in humans so great it can't be dosed) or Phase 2
(where it just shows no effectiveness in humans at all - not even some level
of effectiveness that fails in cost/benefit analysis). this is the problem
with people complaining "But every delay kills people!"

No. You don't know going in whether it's going to work - that's why you're
doing a trial. And from a naive position, the probability is pretty clear that
it's very unlikely it's going to work. There's absolutely no reason to think
any particular drug is worthwhile, and every to worry about its side-effects.
With a sample size of 12, this one may yet became a last-ditch drug with
toxicities worse than chem/rad. We don't know yet. Using this is an example of
over-cautiousness is ridiculous.

Additionally, the slowest part here wasn't the clinical science - it was the
basic science. Gene therapy has been a failure for decades, and we've been
repeatedly going at it to try and get it to work. It's not as though this is
the first clinical trial for a gene therapy: it's just one of the first to be
worth anything.

~~~
nawitus
>Gene therapy has been a failure for decades, and we've been repeatedly going
at it to try and get it to work. It's not as though this is the first clinical
trial for a gene therapy: it's just one of the first to be worth anything.

Glybera is a gene therapy which has been approved for medical use.

~~~
ordinary
Your post is misleading. You're not providing counter-evidence for the
'failure for decades' claim, and are in fact confirming the 'one of the first'
part.

Yes, it has been approved, but only very recently, in late 2012. It is also
the first such drug that has been approved (and to date, the only one), and
this happened under 'exceptional circumstances'. The usual standard of
supporting evidence was forgone because the disease it treats is so rare. The
company is explicitly required to supply further supporting evidence, and the
rules for its use are very strict.[1]

[1]
[http://www.drugs.com/uk/glybera.html](http://www.drugs.com/uk/glybera.html)

------
codezero
I'm baffled by the HN title of this article. There is no place in the article
that claims a 100% success rate for curing leukemia.

The title is: "Has Carl June Found a Key to Fighting Cancer?"

Fighting cancer and curing it are hugely different. Yes, this is a human
interest story that outlines the success of a particular patient using a
particular method, it's great, but it seems disingenuous to use the title that
is here.

~~~
tluyben2
9 out of 12 is also not 100%

~~~
westicle
60% of the time, it works every time.

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aspensmonster
This certainly seems like a very interesting and double-edged sword of a
treatment. The engineered T-cells nuke the tumors, which is a good thing. But
if I'm reading this right, the large amount of cytokine that gets released
from such a rapid destruction also wreaks havoc on your kidneys and could
itself be fatal. It sounds like an all-or-nothing treatment that you either
sweat out or succumb to. Apparently there's a drug (tocilizumab) that
essentially acts as an undo button by taming the engineered T-cells and
avoiding such fatalities, but then you're back to square one. It looks like
the Penn team has partnered with Novartis to study the engineered T-cells and
(I'm guessing) develop a method to tailor the engineered T-cell growth rate to
a magnitude the kidneys can manage.

~~~
ams6110
Wondering why dialysis couldn't be employed to take the load off the kidneys
during the worst of it. Or does dialysis not remove the cytokine?

~~~
VLM
I googled around looking at the opposite direction, are t-cells small enough
to get flushed out by dialysis? Could not get a straight answer. There must be
a lot of money to be made in dialysis; there are a lot of "popular science"
type articles about it. My guess is we'd have to try a level of indirection,
red blood cells aren't lost, so relative size of t-cells vs red blood cells
would probably answer that.

The other idea I have is MDs are not overly dumb, so if its possible for
natural or artificial kidneys to filter the bad stuff to the outside while
keeping the good stuff inside, they would probably just absolutely flood the
patient with IV fluid. The original article was very detailed about the
experience; this didn't make the article, so I don't think they were doing it.

------
lutusp
> Human trials having 75% success rating for curing leukemia

Please do not use the word "cure" when talking about cancer. The article's
submitter invented this headline -- the article doesn't support it in any way.
In fact, it says this: "Scientists don’t talk about “curing” cancer. A cure is
the hope so great, so seemingly out of reach, that it must never be invoked.
They’ve built a wall around the word."

And well they might.

~~~
adaml_623
Not using the word cure is superstitious claptrap.

If I get cancer I want a cure. If anybody in my family gets cancer I want them
cured.

This wariness of using the word cure is just because of the idiots in this
world. People who can't understand percentages and possibilities. People who
believe that anecdotes prove a point.

HN doesn't have to conform to that silliness.

~~~
vidarh
And this is _exactly_ why they don't use the word cure: None of our current
approaches to fighting cancer are particularly good as cures. They remove
enough of the cancerous cells that with luck the cancer won't regrow.

But unlike a lot of diseases where we can usually pretty much guarantee that
we wiped it out, we can usually do no such thing with cancer.

A cure has a vastly stronger expectation.

The day remission is something that happens in so few cases it's a rounding
error, we can start talking about it being a cure.

~~~
VLM
"The day remission is something that happens in so few cases it's a rounding
error"

No, it merely has to be about as reliable as a "cure for pneumonia". It
doesn't have to exceed that limit and approach a "cure for a laceration" or a
"cure for appendicitis" both of which basically don't spontaneously reappear
(assuming surgical removal of appendix)

~~~
lutusp
> No, it merely has to be about as reliable as a "cure for pneumonia".

You're overlooking something very important -- we know what causes pneumonia,
but we don't know what causes cancer. When we treat pneumonia, we're treating
a cause. When we treat cancer, we're treating a symptom.

The reason for "remission not cure" is because we don't have any way to
definitively say there won't be a recurrence, and this will remain true until
we fully understand cancer.

~~~
refurb
Sure we know what causes cancer, uncontrolled growth of a mutated cell!

I see where you're coming from, but the differences between pneumonia and
cancer aren't as great as you think.

If you have pneumonia, they give you an antibiotic. They can test for the
presence of the pathogen, but they can't ever say you are "cured". Take c.
difficile infections. They treat the symptoms, but you can "relapse".

In cancer you can test for the presence of the mutated cells (minimum residual
disease). Often what they'll do is count the mutated cells from a biopsy, and
with this current treatment, the number of remaining cells is less than the
lower limit of detection.

Of course, this is only true in the liquid cancers. Solid tumor cancers don't
work the same way.

~~~
lutusp
> Sure we know what causes cancer, uncontrolled growth of a mutated cell!

That is an _effect_ , not a _cause_. Your claim is like saying that auto
accidents are caused by cars getting too close together. That's only a symptom
of an underlying cause.

> I see where you're coming from, but the differences between pneumonia and
> cancer aren't as great as you think.

We know what causes pneumonia. Because of this, we can suggest behaviors that
will prevent it before the fact, we can identify it unambiguously, and we can
cure it after the fact. This isn't true about cancer -- we don't know what
causes it, therefore we cannot proactively prevent it, we can't identify it
very efficiently (there are always false negatives and positives) and we
cannot cure it. There's no comparison.

> They can test for the presence of the pathogen, but they can't ever say you
> are "cured".

Of course they can. In infectious disease, they can test for the presence of
the causative pathogen -- no pathogen, no disease. In cancer, to do this, we
would first need to identify the cause. But _we don 't know the cause_, we
only know the effect.

> In cancer you can test for the presence of the mutated cells (minimum
> residual disease).

This is like saying we can test for the presence of a car crash by measuring
bent bumpers and inflated airbags. That measures effects, not causes.

> Often what they'll do is count the mutated cells from a biopsy, and with
> this current treatment, the number of remaining cells is less than the lower
> limit of detection.

Counting abnormal cells only reveals how little we know. We detect cancer by
detecting abnormal cell growth. We measure progress in symptomatic treatment
by counting abnormal cells. We declare a remission by making that count
approach zero using agents that kill abnormal cells. There are any number of
cases where the count of cancerous cells was below the limit of detection, but
still caused a recurrence.

In 1979, smallpox was declared to have been globally eradicated. How? By
identifying the responsible pathogen, then systematically destroying it
everywhere it appeared. This was only possible because we know what caused
smallpox, and we could treat the cause, not the symptoms. Because of what we
knew, we were able to call smallpox permanently cured.

We cannot do this with cancer, because we don't know enough about how it
works. All we can do is tell people to avoid risky behaviors, behaviors that,
for often-unclear reasons, increase one's chance to contract this disease.
Then, once the disease's symptoms appear, we have crude methods to deal with
it, like trying to kill the cell masses that represent the disease's primary
symptom.

Based on a comparison with other diseases, cancer treatment is unbelievably
primitive -- it would be like treating a finger infection by cutting off a
person's hand. And guess what? Before germ theory and before antibiotics, that
_was_ the treatment -- cut off the infected limb before the infection spread
through the body.

The reason we don't tell people they're cured of cancer is because of science.
In science, there are no fairy tales -- everything depends on evidence. And we
don't have the evidence science requires to declare cancer cured.

~~~
VLM
This argument appears to revolve around a very unconventional definition of
the word "cure". It may be technically correct inside the oncology community
or related affinity / fundraising industry group to use an alternative
definition, but the original debate was about insiders using the word "cure"
with the general public, where its probably vital to use the general public's
definition as opposed to made up definitions. That said, I typed "definition
of cure" into google and the response humorously was the exact opposite of the
claimed definition, "Verb Relieve (a person or animal) of the symptoms of a
disease or condition" solely focused around relieving symptoms, not total
scientific analysis of the entire situation or root cause analysis or any of
that much more complicated stuff.

Its OK to have a near religious belief in unusual definitions; its just
useless when trying to talk to the general public, especially if they operate
under the logical opposite of your personal definition. I believe this is a
"Startup Lesson". Redefine words for yourself and folks in your affinity group
all you want, but trying it with the general public is likely not to work very
well.

For example of what the general public defines as a cure, examine the
1850-whatever cholera outbreak in London. The prevailing theory of "bad air"
was pretty much blown away when statistical analysis pointed to one particular
water well, which had its handle removed. That outbreak of cholera was
successfully cured, without understanding much other than it had nothing to do
with air and apparently revolved around the use of one particular water well.

~~~
lutusp
> This argument appears to revolve around a very unconventional definition of
> the word "cure".

It's not at all unconventional -- in fact, it is the most common definition,
and cancer doesn't meet it, which is why medical ethicists insist on
"remission".

The point is that, given the public's common understanding of the word "cure",
i.e. that after treatment a particular disease has been eradicated, cancer
cannot be cured, only placed in remission.

> That outbreak of cholera was successfully cured ...

Now you're desperately trying to inject this word into sentences where it has
no place. The cholera outbreak was stopped, but the problem of identifying the
cause remained, just as with cancer. Therefore, no cure -- it's the wrong
word.

Another example would be to respond to a Plague outbreak by moving to the
country, as Newton did. Is that a cure? Of course not -- it's a survival
strategy, but it has no depth or insight.

Remember that Semmelweiss was unable to get doctors to wash their hands, even
though he had excellent statistical support for his suggestion, because he
couldn't explain why his suggestion worked.

> Its OK to have a near religious belief in unusual definitions; its just
> useless when trying to talk to the general public, especially if they
> operate under the logical opposite of your personal definition.

Thank you for making the exact point I have been trying to make, to wit: in
fairness we must pay attention to the public's understanding of this quotidian
term. Most diseases that have treatments in modern medicine, also have cures.
Cancer doesn't. To claim otherwise is to violate medical ethics.

------
krschultz
I would highly recommend "The Emperor of All Maladies" for anyone seeking a
more solid understanding of cancer. I really didn't _know_ much about cancer
and treatments until reading this book, and now I feel like I at least have a
general understanding. I read it after a family friend succumbed to cancer and
I realized that I knew very little about the entire disease.

My take away at the end of the book was that for all of the "war on cancer"
hyperbole going back to the 50s, up until the mid-90s, we just didn't know
enough about cancer to really be fighting it. I feel a lot more optimistic
about the next 50 years of cancer research than the previous 50.

[http://www.amazon.com/Emperor-All-Maladies-Biography-
Cancer/...](http://www.amazon.com/Emperor-All-Maladies-Biography-
Cancer/dp/1439170916/) (non-affliate link)

------
angersock
So, somewhat darkly, when I saw this article a moment ago, it had a claimed
100% success rate. Now it's a 75% success rate.

Did a quarter of the patients just die?

~~~
mrb
The title was edited to reflect the actual success rate (9 out of 12
patients).

------
thucydides
The real headline here: "Has Carl June Found a Key to Fighting Cancer?" If a
headline asks a question, the answer is virtually always "no" or "not yet,"
but the paper wanted to run a story anyway.

[http://en.wikipedia.org/wiki/Betteridge's_law_of_headlines](http://en.wikipedia.org/wiki/Betteridge's_law_of_headlines)

~~~
anonymous
Actually, I was presently surprised that the answer was not the resounding
"no" I expected, but instead a "kind of (for a layman's definition of cure,
for a certain kind of cancer)".

------
dalek_cannes
The article's more about the patients than the science.

I got bored with it so I went and found this, from Carl June himself:

[http://www.youtube.com/watch?feature=player_detailpage&v=1sA...](http://www.youtube.com/watch?feature=player_detailpage&v=1sA_oz_1P5E&t=444)

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ckayatek
Micromet was developing a set of bi-functional antibodies that pretty much
accomplished this same thing. That is directing the immune system to tumors.
One side of the antibody would bind the tumor, while the other bound the
T-cells. They were bought out by Merck a year or two ago and I believe the
therapies are in clinical trials. You can read about the antibodies here:
[http://cancerres.aacrjournals.org/content/69/12/4941.full.pd...](http://cancerres.aacrjournals.org/content/69/12/4941.full.pdf+html)

The added benefit here is that the antibodies can be produced en masse and
delivered as a drug rather than reprogramming the person's T-cells.

------
brador
This is an interesting precursor to curing cancer. What will happen to the
leukaemia industrial complex? The charities? the specialists? the drugs? Will
they all just close shop and go home?

~~~
gargoiler00
Also what about the sudden population explosion? What if the survivors need
after care for the rest of their lives, or expensive drugs?

~~~
anovikov
Leukemia doesn't affect many enough people in reproductive age to cause a
population explosion. Basically, no medical advance can cause population
explosion in the rich world: there are very few people dying from disease in
reproductive ages there. Making people who would otherwise die at 55 live
through 95 does not make a population explosion because they won't have any
kids anyways.

------
jetru
Stories like these not only show that cancer research edges us ever so
slightly towards solving one of the world's biggest problems, but also shows
to us the ever upward curve of human innovation. The path to an engineered
humanity may seem unspiritual and mechanized to some, but to me it expositions
one of the true beauties of our existence - that is, we are our own
antibodies. Stories like these inspire and nurture the best in us. Keep at it
Carl June - you are a true hacker.

------
anovikov
I wonder what happened to those 3 unlucky guys for who it didn't work. Were
they just too physically weakened+had too much tumors to survive the resulting
cytokine storm, leaving the doctors with a grim choice between letting patient
die of cancer by suppressing T-cells too much, or from cytokine storm by not
suppressing them enough? Or there was simply no result from these T-cells,
like they failed to multiply to work, or failed to work after multiplying?

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reubensutton
Would a reduction of 70%, like it cites for one of the failures of the
treatment, cause the patient's condition to improve a bit, or would it be
effectively the same?

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3327
Misleading headline...

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polskibus
Fantastic story, good to hear about people who decide to tackle the hardest
problems. One step closer to understanding and defeating cancer.

