
Patient Number One in a new cancer treatment - dnetesn
http://nautil.us/blog/this-mans-immune-system-got-a-cancer_killing-update
======
byteCoder
Five years ago, I had my own immune system rebooted to (so far) eliminate my
Stage IV melanoma cancer in a trial at the National Institutes of Health. At
that time, without further treatment, I probably had six to twelve months to
live.

In essence, the tumor infiltrating lymphocytes (TIL) adoptive cell therapy was
as follows:

1\. The doctors removed a melanoma tumor that was growing in my neck.

2\. In the lab, white blood T cells (T lymphocytes) that were attempting to
attack the cancerous tissue in my tumor were isolated into at least five
different petri dishes. The white blood cells' growth was stimulated using
IL-2.

3\. Those samples that grew the most and attacked the cancerous tissue (2 of
the samples, in my case) were then expanded to a total of 130 billion
lymphocytes in the lab.

4\. I returned to NIH for a week of immune system preparation, specifically
the almost complete suppression of my own active immune system using harsh
chemotherapy. This was to allow my body to accept the new lab-grown immune
system.

5\. Once my immune system was sufficiently suppressed, I received all 130
billions of the lab-grown lymphocytes. The immune system was then stimulated
by having five large doses of IL-2 every eight hours over a two day period.
(Note: This was hellish.)

6\. After a week or so, my immune system had recovered and I was released from
the NIH Clinical Center to return home. I was given an anti-biotic to take for
4 to 6 months to reduce the possibility of contracting a specific pneumonia
(PCP).

7\. I returned to NIH monthly for scans monthly for the first three months.
After month one, my tumors had shrunk 33%. After month two, 66%. After month
three, they were almost complete gone. My immune systems had essentially been
immunized against some of the mutations contained in my cancerous melanoma
cells.

8\. I was declared NED (no evidence of disease after 15 months) and a complete
responder to the treatment after 21 months.

Now, almost five years post-treatment, I have had CT scans and brain MRIs
every six months with still no signs of melanoma. My doctors have told me that
I'm likely cured.

Immunotherapy works. I chose this trial because the I liked the fact that my
own immune system was being boosted to fight my cancer.

Further info: [https://en.wikipedia.org/wiki/Tumor-
infiltrating_lymphocytes](https://en.wikipedia.org/wiki/Tumor-
infiltrating_lymphocytes)

My doctor is Dr. Steven Rosenberg of the National Cancer Institute.

~~~
byteCoder
Also, besides the overall success of my treatment, other than regular followup
scans, I don't require any further medications of any sort. It's a one-and-
done treatment. I'm certain that Big Pharma doesn't like these treatments.

~~~
epistasis
Congratulations on a successful treatment! It is so wonderful to hear stories
like these. Immuno-oncology is bringing great hope to mutation-rich cancers
like melanoma.

>I'm certain that Big Pharma doesn't like these treatments.

You would be certainly wrong on that part. Immuno-oncology has been "Big
Pharma's" major focus for the past 5-10 years, inspired in no small part by
the work of Rosenburg and many others. One of the most recent approvals
discussed on HN was for a CAR T-cell targeted against CD19. Big Pharma would
also be very happy to sell immune checkpoint inhibitors for use in combination
therapy with adoptive cell transfer.

~~~
byteCoder
I hope that I'm wrong. Many more patients can possibly be saved with more
widespread use of this treatment. Of course, the FDA needs to modernize their
own approval processes to deal with such personalized treatments. It's my
understanding that my lab-expanded lymphocytes needed to be individually
approved by the FDA.

I do know that my specific trial at NIH was sponsored by Lion Biotechnologies
as part of that company acquiring a license to reproduce the laboratory
processing for the TIL ACT.

------
jfarlow
Chimeric Antigen Receptors are an impressive first step into designed
biological technologies. There are new challenges associated with their design
and deployment - but there are also a lot of theoretical capabilities that are
unmatched non-protein therapeutics. It's very much a new paradigm in
treatment. These are 'cures' to human misregulations very much like how small
molecules 'cured' patients of foreign diseases a century ago (and do _not_
cure patients of regulatory diseases).

If you want to build your own chimeric antigen receptors we've built a digital
infrastructure to allow you [1]. Though we just made public our generic
protein design software (thanks ShowHN! [2]), we're employing the same
underlying digital infrastructure to build, evaluate, and manage CAR designs
in high throughput [3]. The drug approved here was painstakingly designed by
hand [4], while we think the technology now exists to permit many more such
advances to be created at a much more rapid pace.

[1] [https://serotiny.bio/pinecone/](https://serotiny.bio/pinecone/)

[2]
[https://news.ycombinator.com/item?id=14446679](https://news.ycombinator.com/item?id=14446679)

[3]
[https://serotiny.bio/notes/applications/car](https://serotiny.bio/notes/applications/car)

[4]
[https://serotiny.bio/notes/proteins/car19/](https://serotiny.bio/notes/proteins/car19/)

~~~
rubatuga
Wow, this seems really amazing. I read some background from your show HN, but
does your software mostly make DNA plasmids? How would you go about
integrating that into a eukaryote? I think in the article they used a
retrovirus. Also, plasmids have a maximum size for proteins, do you have a
vector to incorporate larger proteins?

~~~
jfarlow
The software 'compiles' down to DNA - which can be produced and delivered in
any form useful to clients. Most of the time that deliverable is a plasmid.

The plasmid DNA is then used as a reagent to manufacture the physical
retroviruses that are used to transduce the extracted T-cells which are then
reimplanted into a patient.

Practically, multiple plasmids, each containing a single component of a
synthetic retrovirus are given to 'viral manufacturing cells', and the output
is pool of virus that is infectious only once, and has DNA that encodes the
CAR design as its payload. That virus is then given to the extracted T-cells,
where it infects them with the viral payload and integrates its genetic
payload into their genomes. Once integrated, the cells are tested to ensure
they are not further infectious, then reimplated - newly 'upgraded' with DNA
that encodes a synthetic CAR protein that is now capable of homing in and
killing the target cancer.

Getting all that payload into a plasmid is certainly an art. A lentiviral
capsid has a physical pressure capacity such that it can hold <13kb of DNA.
This is precisely why it's so important to have good ways of
testing/pruning/evaluating new protein designs so that you can prune down a
theoretical design into precisely the minimal design required for effect.

------
rubatuga
Immunology is one of the biggest fields that are stepping up to fight cancer.
In a nutshell, we are programming the patients immune system to kill its own
cancer cells, a marked departure from the general toxic chemotherapy that
weakened almost every dividing cell in the human body. I believe people in a
few decades will look back and express disbelief at the barbaric way we tried
to treat cancer.

~~~
Mz
I would like to see a more elegant means to boost the immune function, without
so much of the Dr. Frankenstein element. I think supporting the immune
function is the way to go, but I think we need a lighter hand, not a heavier
one.

~~~
jfarlow
If you are directing the immune system against cells that the body perceives
as 'self', then simply boosting the system to the point it attacks a cancer
will likely be detrimental the patient. Cancers and other similar diseases are
so difficult to address precisely because they are borne from a patient's own
cells, own genome, and own systems. This therapy here is a very pointed
mechanism to demonstrate to the immune system what is okay to attack, and what
is not - a very particular and specific kind of guidance that a generalized
'boost' would not properly address. And in that way it actually is an elegant,
precisely designed system in play here.

~~~
Mz
_Cancers and other similar diseases are so difficult to address precisely
because_

My general understanding is that they are so difficult to address because we
don't really understand them.

I have a condition that gets partly explained as "overactive immune response."
I really hate the concept of autoimmune diseases and I hope that someday it
will be mocked as "god, what those barbaric idiots believed back in the day."

~~~
jfarlow
'Cancer' is a huge umbrella term. Some cancers we know very well, many we do
not. The one's being addressed by these therapies are well enough understood
to target therapeutically. Some like cervical cancer, skin and lung cancer are
well enough understood to in part be prevented.

But under that umbrella the reason cancers are 'hard to treat' (from the
perspective of a pharmaceutical education/industry/knowledgebase that had a
century of success curing invading diseases) is because cancers do not present
a 'differnece' that can be exploited biochemically. Cancers are by definition
a mashup and amalgamation of the components that make up a human - again very
much unlike a bacteria, viral or fungal infection.

You are correct though that there is still a lot for us to learn. The
technologies in this article are very much a glimpse of the next steps though.

~~~
Mz
That honestly does not fit with my understanding of the problem space. Granted
my understanding of the problem space is as a layperson, not a medical
professional. But I am a layperson who took care of a relative after their
first mastectomy, I have multiple relatives who have had cancer, some of them
repeatedly, and one relative was themselves Patient Zero in a cancer treatment
study. So, it isn't like I have been unexposed entirely to the intricacies of
cancer treatment.

I don't really know how to effectively engage you, but I stand by my initial
statement of:

 _I would like to see a more elegant means to boost the immune function,
without so much of the Dr. Frankenstein element. I think supporting the immune
function is the way to go, but I think we need a lighter hand, not a heavier
one._

I don't really feel you are making points that invalidate that desire. Perhaps
we just don't understand each other. If so, it is probably best to stop here
rather than keep digging a deeper grave.

------
perseusprime11
Why can't we focus a lot of funding on this project? This is exactly the kind
of thing for Government to lead rather than wasting time trying to healthcare
out.

~~~
zackmorris
I agree.

Most people don't seem to realize the kind of progress that's been made in
recent years with CRISPR etc. These problems are becoming data problems rather
than biology/chemistry problems. The public (government) should certainly be
funding many teams with small amounts of money ($10,000 to $100,000 say)
rather than pouring billions/trillions of dollars into "proven winners" (big
pharma) that mainly come up with therapies rather than doing basic research.

Honestly I think the same argument applies to so many areas of the economy:
alternative energy, space travel, growing food, and so on. We could be finding
so many "cures" for relatively modest investments that our current system has
actually become very expensive due to the opportunity cost of not doing so.
I've spent most of my life asking what we are all working for and towards but
have come to the conclusion that keeping everyone busy is the goal now, not
progress.

~~~
deorder
What about the following CRISPR patent problem?

[https://www.forbes.com/sites/jacobsherkow/2017/02/21/how-
muc...](https://www.forbes.com/sites/jacobsherkow/2017/02/21/how-much-is-a-
crispr-patent-license-worth/#3f325ed06b77)

[http://www.nature.com/news/why-the-crispr-patent-verdict-
isn...](http://www.nature.com/news/why-the-crispr-patent-verdict-isn-t-the-
end-of-the-story-1.21510)

This could discourage smaller companies from picking it up (ex. to build upon
it, from which in the long run everyone will profit, see open-source) and make
CRISPR-based treatments more expensive / unavailable (ex. large companies
owning the patents artificially inflating the price, may be even more than the
old technology it replaces).

------
agumonkey
How many of you or people you know would run away from new treatment trials ?
I've been surprised to see a few people getting more than annoyed at
suggesting it. "I'm not a guinea pig" was the recurrent answer.

~~~
Grangar
If you have no options left, I suppose it's the only sensible thing to do.
Either you're 100% sure you die from cancer, or you take an unknown chance
that might save you.

Then again, not all people are very capable of rational thought.

~~~
agumonkey
It's rational in the light of people believing labs are just here to take
advantage of you and try nasty chemicals on you.

------
bitwize
The manga _Hellsing_ features a character named Alucard who is no relation to
the _Castlevania_ Alucard. This Alucard is, in fact, Dracula himself, who was
defeated by Abraham van Helsing and, rather than accept destruction, swore to
be a servant of the van Helsing family, who employ him as a powerful weapon
against the undead.

I mention this because it seems HIV is the Alucard of immunological
treatments: a terrifying incurable disease which we now use as a potent weapon
to fight other diseases. The thing that made it so terrifying -- its tendency
to attack immune cells -- also makes it incredibly fit to purpose.

------
gozur88
I fully expect in 30 years few people will die from cancer, but instead we'll
be dying from things like antibiotic immune staph and strep.

~~~
kevinwuhoo
If we can design CARs for cancer specific markers or have the technology to
create other immunotherapies, I don't see why we couldn't do the same for any
antigen including antibiotic resistant bacteria. A quick search shows that
there is some work in this area already.

~~~
patall
In theory sure, but cancer affects you within month or years, while viral or
bacterial infection hit you in hours or days.

------
mabbo
I'd love to see a comparison done on the news pieces we're reading today about
CAR-T and compare it to the news stories a century ago as penicillin was
discovered and began being used as a treatment.

Everyone is afraid to over-hype this, but take a moment and consider that
we're now re-wiring the human immune system to fight things it previously
couldn't. That's incredible.

Obligatory xkcd on the topic: [https://xkcd.com/938/](https://xkcd.com/938/)

~~~
jfarlow
Penicillin :: invading diseases (bacterial/viral/fungal)

CARs (& protein biotherapetuics) :: human diseases (misregulation/cancer)

------
omegaworks
>leukemia, lymphoma, and squamous cell skin cancer

Whoa... what is the probability that you'd get all of these without being
exposed to a carcinogen?

>retired corrections officer

I wonder if the prison he was working in was built near a superfund site.

[http://www.alternet.org/environment/americas-toxic-
prisons-e...](http://www.alternet.org/environment/americas-toxic-prisons-
environmental-injustices-mass-incarceration)

~~~
URSpider94
They mention in the article that the skin cancer appeared to be a metastasis
from his bones. I expect that all of these cancers stemmed from a single
source in his bone marrow.

