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.
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.
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.
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
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.
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.
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).
"Inactivation of the Ctla4 gene in
mice, performed in the laboratories of Arlene
Sharpe and Tak Mak, confirmed and further
substantiated its negative regulatory role, since
these mice developed very severe autoimmune
disease associated with proliferating T cells (Tivol
et al., 1995; Waterhouse et al., 1995)."
"In the first-in-man study MDX-010 was given to 9
patients in a phase I clinical trial at a single dose
of 3 mg/kg and a response was observed in
some melanoma patients (Hodi et al., 2003). The
same year complete regression was reported in
another trial in some treated melanoma patients,
while severe autoimmune side effects were also
observed (Phan et al., 2003)."
So I wouldn't take it "just in case" like a daily multivitamin. Plus, monoclonal antibodies are expensive!
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!
> 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.
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.
> 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.
It quite often is actually. Until today, about half of all human genes have never been described in any detail at all. We do not know what function they serve, only that they exist and that most of those are probably not that important. Therefore no early career scientist can really dare to investigate any of them, if they do not certainly want to endanger their future careers. If they would have not worry about that, a lot of bright minds that now only study those 5% of genes that promise the most interesting results could diverge and with a high probability discover a new PD-1 here and CTLA4 there. And thats not a question of time (besides the maybe 10 years to study a gene well), that is 100% a problem of funding.
It's not a 100% fit to your point, but there's that old bromide that half of $[stuff] is $[good in some way] and half is $[bad], but we don't know which is which.
> 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.
The US benefits much more from developing cutting-edge weaponry than a cure for a deadly but rare health problem. It should be noted that military programs like the F35 involve both research in many fields of hard science and engineering, and generates demand for highly technical and highly specialized areas of expertise.
These military programs may not cure cancer but improve the lives of a whole lot of people within the US.
The US benefits probably far less from developing cutting-edge weaponry than from curing a deadly but rare health problem that kills a couple of hundred thousand people each year.
It should be noted that scientific programs like cancer immuno therapy involve both research in many fields of hard science and engineering, and generates demand for highly technical and highly specialized areas of expertise.
These scientific programs may not result in the next GPS but improve the lives of a whole lot of people (directly through treatment and indirectly through being paid) within the US.
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.
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.
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.
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.
CRISPR will mostly likely win the chemistry (same as PCR) prize at some point. Maybe Wednesday, maybe in 10 years when the committee can finally decide whether Doudna and Charpetier deserve it more, or Zhang or any of the other scientists involved. Anyways, CRISPR is recognized and will win a nobel, its only a question of time.
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.