HN Gopher Feed (2017-07-19) - page 1 of 10
Patient Number One in a new cancer treatment
97 points by dnetesnhttp://nautil.us/blog/this-mans-immune-system-got-a-cancer_killi...
byteCoder - 2 hours ago
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:
doctor is Dr. Steven Rosenberg of the National Cancer Institute.
kaik - 1 hours ago
This is a fantastic story. I'm so happy to hear that it worked
for you!! Thanks for sharing!
lr4444lr - 1 hours ago
This research and your story give me so much hope for people who
have inoperable cancers and can't handle chemo. I look forward to
the day that we can rank cancer among syphilis, tetanus, and all
of the other past disease scourges of man made completely
eliminable by a non lifelong treatment.
e40 - 28 minutes ago
and can't handle chemoHe said he had chemo to suppress his
immune system before he got the new one.
ABCLAW - 2 hours ago
When I used to work in a lab, these types of reports were common
and delightful to hear, but very few patients were as well
informed and granular with their understanding as you
are.Congratulations on your recovery!
Mz - 1 hours ago
I chose this trial because the I liked the fact that my own
immune system was being boosted to fight my cancer.We need more
of this.Congrats on being NED.
byteCoder - 2 hours ago
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 - 2 hours ago
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 - 56 minutes ago
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 - 10 minutes ago
Yep. Novartis' new CAR was recommended for approval last
week. ~100 are in the FDA pipeline, and now that the first
was unanimously approved, expect a lot more.Paywalled, but a
good review of the 100 in trials right now:
xxSparkleSxx - 17 minutes ago
>I chose this trial because the I liked the fact that my own
immune system was being boosted to fight my cancer.I work in
biotech and a very successful CEO of mine once told me "When I'm
evaluating new (bio)technologies, always bet on tech that
replicates/take advantage of a currently working biological
system. Tech where everything is synthetic/relies on a custom
designed system/etc is much more likely to not work in the long
pryelluw - 14 minutes ago
I just lost my mother to cancer and it was a hellish experience.
It gives me joy to know someone out there beat it and that people
in the near future may have a better chance than mom did.
Congratulations on the recovery. Wish you many wonderful years
full of life!
QAPereo - 2 hours ago
Re: The IL-2 infusions being hellish, I can guess why that would
be (pain, fever, delirium, and so on), but I'd be interested in a
first-hand account from someone like you, who seems to be so able
to communicate these experiences. In short, what was the hellish
part of it?
byteCoder - 2 hours ago
You've listed the main side effects of the treatment: pain,
fever, and delirium.About 20-30 minutes after receiving a dose
of IL-2 by infusion, my body would undergo violent bed-shaking
rigors for 10-20 minutes. I had the worst chills I've ever had,
followed by breaking out in a hot sweat when it had passed.
This was very unpleasant.After each successive dose, the
effects would worsen.Essentially, the doctors were trying to
take my body to the brink of experiencing a cytokine storm
(https://en.wikipedia.org/wiki/Cytokine_storm) to jump-start my
immune system.This was a pretty miserable part of the
treatment, but (in the end) obviously worth it.
QAPereo - 1 hours ago
Wow, that's absolutely incredible, thanks for the answer, and
let me say how glad I am that you're still around to offer
hughes - 44 minutes ago
That's an incredible story, thanks for sharing.
elorant - 2 hours ago
If I'm not too indiscreet, mind if I ask how much did the whole
byteCoder - 2 hours ago
Since this was conducted under a research trial by the US
government, the treatment did not cost me (or my health
insurance) a penny.I am told that the treatment and follow-ups
cost the research program budget at least a million dollars per
slantedview - 1 hours ago
An important example of the government's role in medicine.
byteCoder - 55 minutes ago
wyager - 11 minutes ago
Many research trials are privately funded, but run by the
government for regulatory reasons. I don't know about this
credit_guy - 17 minutes ago
This is a mind blowing amount. What could be the reason for
such a high cost?
wyager - 8 minutes ago
Cutting edge scientific research is expensive. I don't know
why people expect advanced medicine to be cheap.
Synthesizing or extracting complex proteins, using rare
medical radioisotopes, medical scanners based on the most
cutting edge engineering and physics... Almost no endeavor
besides physics and medicine makes regular use of
superconductors, antimatter (for PET scans), etc.
mullen - 2 hours ago
I thought trials are free. This is prevent "snake oil salesmen"
from trying to sell cures that are not.
PeCaN - 1 hours ago
Woah. That is seriously cool, that we can do that.
Congratulations on your recovery, and thanks for going through
that for science.Can you maybe elaborate a little on how they
selected the cells to lab-grow? Step 2 and 3, in particular. By
what criteria did they divide them between petri dishes and how
did they test how efficient they were at destroying cancer cells?
(Did they feed them parts of your tumor or something?)
jfarlow - 21 minutes ago
Here is a figure that illustrates the process for the CARs in
the article (which is slightly different than OPs, but similar
in result): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC448036
7/figure/...Essentially it has 3 parts:- Extraction of tumor to
test against.- Extraction of immune cells, to which a genetic
therapy is applied that grants them a new tool to home in on
the above tumor.- After testing the immune cells against the
extracted tumor, reimplant the 'upgraded' immune cells.
byteCoder - 54 minutes ago
I don't know all the technical measurements and details, but,
yes, the researchers did feed them parts of my tumor.
perseusprime11 - 21 minutes ago
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 - 8 minutes ago
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.
bitwize - 2 hours ago
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.
jfarlow - 47 minutes ago
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 . Though we just made public our
generic protein design software (thanks ShowHN! ), we're
employing the same underlying digital infrastructure to build,
evaluate, and manage CAR designs in high throughput . The drug
approved here was painstakingly designed by hand , while we
think the technology now exists to permit many more such advances
to be created at a much more rapid pace.
rubatuga - 8 minutes ago
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
jfarlow - moments ago
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 used to produce 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 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.
rubatuga - 2 hours ago
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.
zzalpha - 1 hours ago
Well, the flipside is that if you stop chemo, the damage to your
body stops.But if the immune system over reacts, it can run out
of control and kill you.I have a relative with stage IV melanoma.
She was included in a research trial that used a pair of immune
stimulating drugs in an attempt to get her own body to fight the
cancer.What they didn't realize is she had a latent, undiagnosed
autoimmune condition called vasculitis.Unfortunately, while
vasculitis is normally isolated to a particular part of the body,
hers was systemic. What followed was an immediate halt of the
drug regimen and massive doses of steroids to get it under
control. If that hadn't have worked, it would have killed her.
Full stop.The condition is now fortunately under control, but she
has 30% kidney function, and the steroids pushed her over to full
non-insulin-dependent diabetes. She's now on a targeted therapy
that, for now, has pushed her into full remission, but it's only
a matter of time before the melanoma becomes resistant to the
drug.The reality is, doctors do not fully understand the immune
system. Period. These treatments are in many ways astonishing,
but they can turn frightening very very quickly. And they don't
always work, either.Unfortunately, there are no miracles, here.
lr4444lr - 53 minutes ago
That's true, but assuming this specific treatment doesn't
reprogram the native immune system, it sounds like the side
effects are much shorter and less devastating than the systemic
damage of chemo, even if requiring repeated attempts.
Mz - 47 minutes ago
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.
dekhn - 2 hours ago
or express disbelief that we didn't anticipate outcome> as an unexpected side effect of immune system
tailoring. is likely to be "large
increase in incididence of autoimmune disorders"
rubatuga - 2 hours ago
Well if you use antibodies, they should be able to slowly be
excreted and broken down after a while. I don?t believe
antibodies undergo any memory effect. If you use a specific
form of T cells, they should undergo the same degradation,
although I guess there is a possibility that in some unknown
cases it might revert to a memory cell, although to my
knowledge this doesn?t happen. Lastly, since the virus used to
express the receptor should only infect the cells extracted
from his blood, any autoimmune response shouldn?t last (since
cytotoxic T cells don?t last forever). The virus isn?t self
replicating, and isn?t used to infect any other cells.
dekhn - 1 hours ago
thats a lot of "shoulds" for a complicated system.
rubatuga - 30 minutes ago
I don?t believe you have a compelling argument, any
biological organism has a degree of unpredictability, but
with a series of molecular checks and controls, it becomes
predictable, almost deterministic. Think of how the brain
works, how you have billions of cells acting the way they
?should?, and acting in a predictable way allowing you to
perform daily tasks. I agree we have a lot to learn and
that some mistakes might be made, but that?s what testing
and clinical trials is for.
reasonattlm - 2 hours ago
Which might be controlled by immune ablation; safer targeted
forms of destroying all immune cells would be a very good way
to stop all forms of autoimmunity, and would act as a good
backstop to immunotherapies in general.Right now immune
ablation is pretty rough chemotherapy, but has nonetheless been
shown to put multiple sclerosis and type 1 diabetes into
remission. There are new approaches to targeted cell killing
under development now (such as Oisin Biotechnologies' system)
that should be much better, with minimal side-effects. Couple
that with a cell therapy to accelerate replacement of immune
cells and it looks pretty promising.
mabbo - 2 hours ago
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/
jfarlow - 29 minutes ago
Penicillin :: invading diseases (bacterial/viral/fungal)CARs (&
protein biotherapetuics) :: human diseases (misregulation/cancer)