
James P Allison and Tasuku Honjo win Nobel prize for medicine - okket
https://www.theguardian.com/science/2018/oct/01/james-p-allison-and-tasuku-honjo-win-nobel-prize-for-medicine
======
dm319
That's great. They discovered the CTLA4 and PD-1 receptors - cell pathways
that help protect against auto-immunity and allergy, but which can be hijacked
by cancer to prevent cancer clearance.

The realisation that our immune system is important in protection of cancer is
only really just starting to blossom, and there is a lot that still isn't
understood. We don't know how many cancers are routinely cleared by our immune
system. Some researchers think it might be in the order of 10s a day.

~~~
rqs
So if my understanding was correct, by applying the treatment (Immune
Checkpoint Therapy I guess), immune system will clean cancer cells like
they're doing a everyday task?

Well, then I hope one day that treatment will become cheap enough so it can
benefit everybody.

~~~
iskander
The immune system is thought to already clear mutated and defective cells as
part of their everyday activity.

Cancers which grow to a detectable/dangerous population have to find some way
to evade this immune surveillance and hitting off switches like "immune
checkpoints" is one way to accomplish this. So, blocking the off switches
helps the immune system resume its everyday task of killing weird cells.

~~~
lmkg
Is this envisioned as a treatment for detected cancer, or a preventative
measure, or is the discovery too recent to tell at this point?

~~~
jfarlow
This is already being deployed in therapies today -
[https://en.wikipedia.org/wiki/Checkpoint_inhibitor](https://en.wikipedia.org/wiki/Checkpoint_inhibitor)

And it works well in conjunction with other therapies that guide or otherwise
help the immune system find the cancer. In particular, a style of designer
gene therapy just approved by the FDA, of which one is called a Chimeric
Antigen Receptor -
[https://en.wikipedia.org/wiki/Chimeric_antigen_receptor](https://en.wikipedia.org/wiki/Chimeric_antigen_receptor)

These are in patients now, and curing people today.

If, for instance, the chimeric receptor (a designed synthetic cell-receptor)
is able to enable immune cells to better _sense_ the cancer, and that is
coupled with the checkpoint inhibitors to prevent the cancer from disabling
those immune cells, one's own immune cells will then be able to directly kill
the cancer.

The checkpoint inhibitors (associated with the Nobel here), take the brakes
off of the immune system. This can of course be dangerous, but generally one
of cancer's first tricks it learns is how to apply those brakes to hide from
detection. So by tuning down the sensitivity to the immune system's 'brake
pedal', one's own immune system becomes more capable in fighting cancer.

~~~
iskander
Maybe helpful for the HN crowd: the adaptive immune response typically
prioritizes a low false positive rate. A developing cancer sneaks by as a
false negative. Checkpoint blockade moves the immune system to a regime of
higher sensitivity, at the expense of potentially lower specificity.

~~~
teekert
Yes, this. The side effects are not to be underestimated (they are similar to
autoimmune disorders). Moreover, there are no good tests yet that can predict
whether someone will respond. If someone does, it's sometimes spectacular but
with all therapies from the field combined optimally, less than 40-50%
responds (with single drugs it's around 10% I believe).

------
vincnetas
Why not link to the source of information (with summary, explanation and
illustrations to for common people):

[https://www.nobelprize.org/prizes/medicine/2018/prize-
announ...](https://www.nobelprize.org/prizes/medicine/2018/prize-
announcement/)

------
mxuribe
Obvious cancer treatment aside, I'm amazed about the possibilities for
treating allergies. Sure, allergies might not seem as big a deal, but with the
last few American generations having to deal with - what seems like a crazy
increase in manifestations - from mild nasal/environmental allergies all the
way to severe, deadly anaphylaxis-type (such as vs. peanut and other food)
allergies...I sure hope this area of research gets tons of money thrown in.

Don't mean to get political, but when many U.S. administrations talk of
throwing billions towards military weapons, but nowhere near as much towards
positive research like this, it just gets me frustrated. (Caveat: I do
understand and support __some __types of military research that lead to
positive technologies such as GPS, etc. I 'm referring to governments spending
billions on stupid projects like the F-35 joint strike jet fighter.)

Anyway, kudos and hearty congrats to the Nobel winners!

~~~
jbob2000
> Don't mean to get political, but when many U.S. administrations talk of
> throwing billions towards military weapons, but nowhere near as much towards
> positive research like this, it just gets me frustrated.

I picked up an adage from an old engineer once:

“It doesn’t matter how many men or how much money you have, it still takes 9
months to make a baby”.

I do agree that science is underfunded, but sometimes money isn’t the problem,
things just take time.

~~~
mikeyouse
It strikes me that the "9 months to make a baby" applies much more to
Engineering than it does to Research Science.

There are a ton of areas of research that we know will yield a lot of future
benefit but since the NIH is actually funded at a lower inflation-adjusted
rate compared to 15 years ago [1], the research is held up greatly. Grants to
young scientists are diminishing and many promising researchers are leaving
the field.

Building a bridge is a serial process, studying the metallurgy of hundreds of
compounds is massively parallel.

[1] -
[http://faseb.org/portals/2/images/opa/FederalFunding/Graph%2...](http://faseb.org/portals/2/images/opa/FederalFunding/Graph%202.jpg)

> _From FY 2003 to 2015, the National Institutes of Health (NIH) lost 22% of
> its capacity to fund research due to budget cuts, sequestration, and
> inflationary losses._

------
Insanity
There's also a link to live-reporting:
[https://www.theguardian.com/science/live/2018/oct/01/the-
nob...](https://www.theguardian.com/science/live/2018/oct/01/the-nobel-prize-
in-physiology-or-medicine-2018-live)

~~~
Brakenshire
James P Allison on the harmonica!

[https://www.youtube.com/watch?v=pPsjsdNsdgs](https://www.youtube.com/watch?v=pPsjsdNsdgs)

------
vedtopkar
Amazing and very well deserved! Checkpoint blockade drugs are in their
nascency, and though they aren't a silver bullet, they can be incredibly
effective nonetheless. A large number of people will be saved from cancer (and
maybe some other ailments too) thanks to these scientists.

As an aspiring medical researcher, stories like these are humbling and
inspiring.

------
iskander
Surreal to be at the CRI / cancer immunotherapy conference while this got
announced.

~~~
Gatsky
Yes, I’m there too, feels like we are participating in history.

------
AtlasBarfed
This certainly is promising, but I fear the drug companies will block the
customized processes that would make this truly useful for mass produced pills
of less efficacy.

I think there are lots of medical treatments involving custom genetics that
might not be as profitable as drug production but would rather involve a lot
of lab work. Things that are initially not as easily automated and profitable
(but certainly economically feasible given the prices of drugs imposed by
patent monopolies).

I don't think investment in these approaches will occur without government
sponsorship and kickstarting.

------
bawana
I wonder what the effect on some psychiatric diseases will be? Recently it was
reported that bone marrow transplant resolved schizophrenia in a cancer
patient.

------
beautifulfreak
I wonder how long it will take for CRISPR to be recognized.

~~~
sndean
Possibly soon. Some awards that Allison/Honjo and CRISPR researchers have both
won recently:

Warren Alpert Foundation Prize: Allison, Honjo et al. (2017). CRISPR
researchers (2016).

Tang Prize: Allison, Honjo et al. (2014); CRISPR researchers (2016).

Albany Medical Center Prize: Allison et al. (2018); CRISPR researchers (2017).

Gairdner Foundation International Award: Allison et al. (2014); CRISPR
researchers (2016).

Gabbay Award: Allison (2011); CRISPR researchers (2014).

Breakthrough Prize in Life Sciences: Allison (2014); CRISPR researchers
(2015).

That doesn't mean they'll win the Nobel, but they're definitely in the same
awards realm recently. It might be Emmanuelle Charpentier, Feng Zhang, and
Jennifer Doudna.

