
Harnessing the Immune System to Fight Cancer - e15ctr0n
http://www.nytimes.com/2016/07/31/health/harnessing-the-immune-system-to-fight-cancer.html
======
Steeeve
My dad was an immunologist.

By all accounts he was absolutely brilliant. I lost him the day after my 9th
birthday in 1982. I grew up with a series of George Washington Cherry Tree
kind of stories about him permeating everything.

There's a lot of pressure growing up being the only son of a very accomplished
person - having the responsibility of filling shoes that just can't be filled.
It got to the point where I started being skeptical. Nature of being a
teen/young adult I suppose. In the mid-90's I was having a conversation with
my Uncle and he tells me how before he died, my Dad was hell-bent on the Nobel
prize. He was going to win it by curing cancer. He told me "the key is in the
T-cells. He was always 20 years ahead of his time." I took it with a grain of
salt at the time. Another tall tale.

Some years later in 2002 I'm reading an article and lo and behold there's
promising research coming around that T-Cell treatment is yielding positive
research in cancer. And now I read this article, scroll down a little, and
there's a diagram highlighting the T-Cell.

A few years after that I end up working at Stanford and that gave me access to
old news articles that aren't up on the web, and a lot of scholarly things
that aren't typically in search engine results. I was absolutely floored to
discover that the tall tales weren't tall tales at all. They were just stories
from people who were honestly proud of him and what he did (even if they
didn't understand most of it). I tracked down a few of his colleagues and I'll
tell you - it was pretty powerful hearing from some very accomplished people
about the work that he did and the kind of man he was.

When you think about it, there has been more progress in medicine in the last
80 years than in the previous 800. It's pretty stinking amazing if you ask me.
And most of it has been made by people who's names you'll never hear or read
about.

This article brought a lot of memories back to me so I thought I'd share. Miss
you dad.

~~~
mailshanx
What's your dad's name? Do you have any material we can read?

~~~
Steeeve
Steven Bix Kallestad - here's a blurb from early on when he developed a
Hepatitis test:
[https://news.google.com/newspapers?nid=2245&dat=19701221&id=...](https://news.google.com/newspapers?nid=2245&dat=19701221&id=CVszAAAAIBAJ&sjid=iDIHAAAAIBAJ&pg=3326,7065893)

Here's an article about his baboons escaping:
[https://news.google.com/newspapers?nid=1798&dat=19660131&id=...](https://news.google.com/newspapers?nid=1798&dat=19660131&id=4PUeAAAAIBAJ&sjid=AIwEAAAAIBAJ&pg=1941,4002263)
(he rescued them from a research facility, they lived in his bathroom while he
was at work, they escaped and lived in the trees outside for a few days)

His public (amex) company getting sold to a private entity shortly after he
died: [http://www.nytimes.com/1982/06/03/business/company-news-
kall...](http://www.nytimes.com/1982/06/03/business/company-news-kallestad-
labs-to-be-acquired.html) (edited because I originally linked to a consecutive
sale)

His products _still_ on the market: [http://www.bio-
rad.com/evportal/evolutionPortal.portal?_nfpb...](http://www.bio-
rad.com/evportal/evolutionPortal.portal?_nfpb=true&_pageLabel=search_page&sfMode=search&sfStartNumber=1&clearQR=true&js=1&searchString=kallestad&database=productskus+productcategories+productdetails+abdProductDetails+msds+literatures+inserts+faqs+downloads+webpages+assays+genes+pathways+plates+promotions&tabName=DIVISIONNAME)

And by the way... his patent on the mouth guard (he was a hockey player and
one day decided people shouldn't lose so many teeth so he put this together
with a friend)
[http://patents.justia.com/patent/3943924](http://patents.justia.com/patent/3943924)

There's a whole world of things that he did and obviously there were a lot of
other scientists involved, but suffice it to say that he had a hand in many
advancements that are taken for granted today like STD tests and treatments,
pregnancy tests, etc. He helped develop and improved a lot of equipment as
well. A lot of the links I can find right now mention Kallestad products used
in research like immunoassays, HGH, nephelometers, etc, but honestly it gets
above my comprehension level pretty quickly. I can point to "page 273 of x
research article where it mentions a specific product/patent/procedure that
the research relied on, but it's not all that interesting if you aren't in the
field (I don't think).

My favorite story about him is about an aligator named Zago. My Uncle lived in
Florida and decided on a whim to send my dad a live alligator. My dad, being a
scientist and used to receiving shipments of animal based serums saw the label
on the box and put it in the refrigerator. Days later, my Uncle called and
asked him how he liked the new pet. He ran to the refrigerator and it was
still alive and kicking. He kept it in the bathtub for a few years until it
got too big and donated it to a zoo.

~~~
mailshanx
That's a really cool story, thanks for sharing! Your dad has such a large and
wide body of work that lives on even today. That's really amazing.

------
jjhammerb
Our lab ([http://www.hammerlab.org](http://www.hammerlab.org)) solves
computational problems in the domain of cancer immunotherapy. Our open source
software ([https://github.com/hammerlab](https://github.com/hammerlab)) is
used to create personalized therapeutic vaccines that we are testing in a
phase i clinical trial right now.

If you are an experienced machine learning engineer and would like to help
improve the quality of our vaccines, please send me an email at hammer at
hammerlab dot org. We are located in NYC.

~~~
LeicesterCity
I'm a recent Biology undergrad. Do you have any advice for learning Comp
Bio/Bioinformatics? Can it be self-taught, or does one need a PhD?

~~~
sn9
It can definitely be self-taught!

A promising path would be to self-teach as much as possible and then apply for
an MS program in bioinformatics or something similar.

Apart from the usual advice for teaching yourself programming, you can
practice bioinformatic-specific skills at the wonderful Rosalind Project [0].

[0] [http://rosalind.info/about/](http://rosalind.info/about/)

------
throwaway945232
I'm a multiple myeloma patient, and started daratumumab a few months ago,
which is a monoclonal antibody. It's not a checkpoint inhibitor as described
in OP, but rather binds to CD38 which is overexpressed by MM cells, and
thereby activates the immune system against those cells.

Certainly activating the body's own defenses against cancer cells seems like
an effective approach. Side effects are minimal as the therapy is more
targeted, but as the article mentions, we just don't understand enough right
now about when they will fail or why they fail.

My own results on dara have been underwhelming. The first month raised our
hopes of a complete response, but it totally flat-lined by the second month.
By month 3 levels were rising again, and now it seems I've bred a more
resistant clone. My next stage of treatment may very well include a CAR-T
based therapy, or a checkpoint inhibitor.

One thing the article gets wrong is the cost. Insurance pays up to $10k per
infusion, but co-pays are capped at < $10k per year. There is a huge market
for these novel agents, and insurance companies are on the hook to pay for FDA
approved treatments. From what I can tell this is driving massive R&D
investment and a large pipeline of new potential treatments.

~~~
atomical
Just curious, why the throw away account?

~~~
throwaway945232
I guess that's one nice thing about chemo that doesn't make you lose your
hair, cancer isn't really part of my public identity. Of course my close
friends and family know, a few work colleagues, but for now at least that's
the extent of it. I guess I have a keenly evolved defense mechanism of just
not dwelling on shit I can't handle, and not sharing that particular fact
means it doesn't become a part of _every_ conversation. For now anyway, it's
just not something I would want to show up on Google tied to my nick.

~~~
icantdrive55
You shouldn't even have to respond to that question.

I guess I'm getting older, or from a different generation, but a lot of life
is personal--right?

I'm shocked at how fast Google scoops up these posts for the world to see
forever. There been times where I go back to edit/delete a comment, and figure
what's the point; Google set it in stone.

~~~
reitanqild
Part of why I love HN: pseudonymous and throwaway accounts allowed + sane
community moderation.

Discussing certain things under full name would almost be irresponsible for
some people as long as Google, Facebook and various TLAs in both the East and
the West has this landgrab going.

------
WhitneyLand
One of the heroes of the article explained how his team discovered the first
drug to prolong survival in advanced melanoma patients:

The discoveries that led to the drug, Dr. Allison said, came entirely from
years of basic research in immunology — experiments in test tubes and mice —
and not from the clinical or “translational” science, aimed at moving rapidly
into humans, that is so heavily favored now by institutions that pay for
studies.

“None of this came from cancer research, none,” Dr. Allison said, adding that
without support for basic research, “progress, if any, will be incremental,
not a big leap.”

~~~
jessriedel
I keep getting hints that there is some fight behind the scenes in US biology
over how much money should be devoted to exploratory vs translational
research. Comments like these pretend as if this wasn't a difficult trade off,
that we need a huge shift in one direction, and that this direction is so
obviously better we don't even need to discuss the relative amounts involved.

------
tominous
The problem with current immunotherapies is that they can trigger a wide range
of auto-immune side effects: skin, lungs, gastrointestinal, thyroid,
pituitary, liver, and more. Each dose is like spinning a roulette wheel and
hoping it lands on "cancer cell" instead of a useful organ.

These side effects can often be dampened with high dose steroids, but they can
persist for a very long time. After all, that's why immunotherapy is so
exciting, it creates a durable response via immune memory.

In my opinion the next big step will be injecting drugs like ipilimumab
(Yervoy) plus adjuvants directly into solid tumours and malignant fluids. This
would lower the total dose, reducing the chance of systemic side effects,
while still delivering a high concentration where it is needed most: where
dendritic cells carrying tumour antigens meet T cells in the nearest lymph
node. The subsequent immune response will still provide a systemic benefit.
For example, a recent melanoma study saw an abscopal (distant) response in 10
out of 12 patients with intra-tumoral treatment with ipilimumab + IL-2, with
no serious distant side effects [1]. (Yes this is a very small study, but bear
in mind response rates to systemic ipilimumab are normally more like 15%.)

Unfortunately I wouldn't expect a company like Bristol-Myers Squibb to fund
these kind of studies. The current model for pricing is by the mg, and intra-
tumoral treatments use about 100 times less product than systemic treatments.

Other drugs like nivolumab/pembrolizumab would still need to be delivered
systemically because they operate on the front-line where T cells meet cancer
cells.

The step after intra-tumoral treatment will be generating and amplifying the
immune response in a test tube instead of in the body. This is also very
promising. [2]

[1]
[http://www.ncbi.nlm.nih.gov/pubmed/27391442](http://www.ncbi.nlm.nih.gov/pubmed/27391442)

[2]
[http://www.ncbi.nlm.nih.gov/pubmed/26894495](http://www.ncbi.nlm.nih.gov/pubmed/26894495)

~~~
epmaybe
My dad was telling me how interventional radiologists have been doing chemo
embolization, where they deliver the chemotherapy directly at the tumor
site/organ. I don't see why they couldn't use ipilimumab and similar drugs to
do the same with immunotherapy.

------
benevol
Wim Hof (aka "the Iceman") has developed a fascinating method which enables
anybody to consciously manage one's immune system, no drugs involved
(scientific studies are available).

This should interest everyone who's dealing with immune system overreactions,
such as any auto-immune disease, allergies, etc. and persistent inflammation
issues (also touching depression).

For an easy intro, check out the Vice documentary:
[http://www.vice.com/en_uk/video/iceman](http://www.vice.com/en_uk/video/iceman)

Joe Rogan has a long interview with Wim Hof:
[https://www.youtube.com/watch?v=Np0jGp6442A](https://www.youtube.com/watch?v=Np0jGp6442A)

A more recent interview: [http://www.richroll.com/podcast/the-iceman-wim-
hof/](http://www.richroll.com/podcast/the-iceman-wim-hof/)

For the biological explanations:
[http://www.icemanwimhof.com/files/2016wimhofmethod-
revealed....](http://www.icemanwimhof.com/files/2016wimhofmethod-revealed.pdf)

One of the scientific studies:
[http://www.icemanwimhof.com/files/pnas.pdf](http://www.icemanwimhof.com/files/pnas.pdf)

Wim Hof's 2 Websites:
[http://www.wimhofmethod.com](http://www.wimhofmethod.com) and
[http://www.icemanwimhof.com](http://www.icemanwimhof.com)

If you don't have the USD 200.-- for the 10 week program, you'll find it on
your favorite torrent site.

------
ohanyan
We're a Start-up building software for this new emerging cancer treatment.
Looking for strong engineering talent. At Vitruvian Networks
([http://vineti.com](http://vineti.com))

------
reasonattlm
The future of cancer is targeting, in one way or another. It has been
interesting to watch immunotherapy win out as the dominant approach to
targeting; there are other options, such as nanoparticle platforms in which
targeting and kill mechanisms could be assembled as needed, or oncolytic
viruses, and so forth. All of those are still under development, just with
nowhere near as much backing as, collectively, goes to forms of immunotherapy.

Still, most immunotherapies packaged and deployed to trials are more of the
same in terms of being very specific to specific types of cancer. There are
hundreds of types of cancer, depending on how you want to count. It is much
better to be able to build a therapy with few side-effects, given that
chemotherapy has a very unpleasant effect on health and life span over the
long term even when successful, but the extreme specificity is still
problematic from the strategic point of view. The cancer community has shown
that they can't produce new therapies for all cancers at a fast enough rate to
completely control cancer any time soon. The strategy needs to shift to
producing therapies that can target many types of cancer.

Once class of immunotherapy shows particular promise on this count, and that's
the chimeric antigen receptor approaches that have produced such good results
for leukemia. It should considerably reduce the cost of building new therapies
for many types of cancer once a couple of types of cancer have been
successfully treated that way and the basic platform is defined. We'll see how
that goes over the next fifteen years or so. All in all, immunotherapies look
to be the replacement for chemotherapy / radiotherapy as the coming generation
of cancer therapies, and people will keep their hair, and will get treated as
outpatients in clinics, and cancer survivorship will increase, and it is
likely that they won't lose a decade of life expectancy as a result of
treatment.

It is worth looking beyond that, however, as the technical basis for the
generation of therapies after immunotherapy is actually being worked on today.
For my money the thing that comes after immunotherapy will involve blocking
telomere lengthening, as that is a - possibly the only - basis for a universal
cancer therapy. All cancers need to lengthen telomeres, cannot evolve their
way around that need, and building one therapy to control every type of cancer
seems a much better path forward than the present strategy of seeking ever
more specific biochemistry to interfere with. A fair number of people are
working on the telomerase side of that equation, and not enough people are
working on the alternative lengthening of telomeres (ALT) side of that
equation, but this will all come to a useful conclusion somewhere in the late
2020s, I'd imagine.

~~~
madengr
I thought telomeres lengthening was for curing old age? Latest issue of
Science News is on age extension; I'm a layman.

~~~
Omniusaspirer
Cancer genesis relies on a sequence of genetic mutations occurring and has
many defining characteristics. The telomere lengthening he's discussing is a
mechanism by which cancer cells make themselves "immortal".

~~~
madengr
So the goal is to lengthen the telomeres if healthy cells and shorten them for
cancerous cells. Will be interesting to see how it works out for Elizabeth
Parrish:

[http://arstechnica.com/science/2016/04/ceo-tests-crazy-
genet...](http://arstechnica.com/science/2016/04/ceo-tests-crazy-genetic-
therapy-on-herself-claims-it-added-20-years-of-life/)

------
mSparks
These treatments are truly awesome.

The pharmaceutical companies now making them.... not so sure.

It makes me generally very angry that nearly all the research has been
conducted using charitable donations and a large volume of open source
software.

then a few pharmaceutical executives get to charge either the insurance
company or in many cases in the US the patients family - hundreds of thousands
of dollars a month to provide access to treatment.

