Very interesting finding indeed, these T cells seem to (not fully confirmed) target cells with abnormal mrtabolism, which is one of the hallmarks of cancer in general (most cancers at least).
This solves one of the biggest problems with immunotherapy, which is that if a cancer is not different from regular tissue in any fundamental way that the immune system cannot recognize, then it can't fight it. This is why melanoma is the poster child of immunotherapies (skin cells get mutated a ton due to UV so skin cancer has a lot of mutations to differentiate it by). If this cell stands further scrutiny, it could potentially be a very general therapy option indeed.
Potential caveat is that cancers typically find a way to generate resistance, and markers of abnormal metabolism (at least as detected by this MR1 receptor) night be easy to suppress, in which case this might just become one in a line of multiple treatments. That might still be good enough though.
Resistance is a neat thing.
I remember (and I'm sure someone will reply with a link to it, since I can't find it) reading a story about a fellow with a very seriously antibiotic resistant bacteria infecting his chest. It resisted everything they had. Researchers found a phage that would attack that specific bacteria- but alas, the bacteria became resistant to the phage as well!
Fortunately, the bacteria had limited dimensions in which to change. The changes needed to become resistant to the phage made it no longer resistant to at least one of the antibiotics. It could not have its cake and eat it to. With both attacks against the bacteria ongoing, it was defeated.
What I'm implying with all this is that yes, the cancer may become resistant to this therapy in question but in doing so it may be forced to become less dangerous, or less resistant to other forms of attack. It does not change merely from "not resistant" to "resistant" but from "form A, which is not resistant" to "form B, which is resistant", and "form B" may have a lot of other consequences.
Even more interesting are drug holidays: cancer becomes resistant to drug A by evolving a new clone that uses some other metabolic pathway unaffected by the drug but is less efficient. Stop drug A, the first more efficient clone takes over again. Give drug A again and there is no resistance for a while.
> deploying phages can cause the bacteria to evolve in response, and that evolution sometimes involves switching from being antibiotic-resistant to being sensitive to antibiotics.
There's a few big stories like this. Chances are, in the next 25 years you may find yourself being treated with phages.
For that reason it seems wrong to think about cancer as “developing” resistances - I don’t believe that cancer is something that evolves/mutates.
It may well be the definition factor, at least some people think so: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941741/
If I remember their argument correctly, cells that "only" reproduce anarchically present little danger (benign tumor) if they don't also do so at an abnormally fast rate / metabolism.
The cancer I had when I was young, Hodgkin Lymphoma, is one extra rule broken because the lymphatic cells already don't stay in one place and makes extra copies of themselves - which is why it relatively often occurs in young people. One copying error and the "Die when told to" feature breaks in the new copies and now you've got cancer.
In that spirit, subsequent mutations that confer resistance can be seen as a consequence of this abnormally high metabolism rate that overwhelm the system and also cause increasing mutation rates.
In conclusion, while cancer may indeed become a complicated condition to treat, the root cause thus defined is rather simple. Whether this paradigm is valid and useful is an open question, but the article being discussed sure seems to point that way.
Immune cells are already resistant to each other, and especially to stress. Additionally, they have pieces of genetic code that are manipulated during their life and potential to become self-reactive with no activation.
If they lose anergy and apoptosis, it can be enough, and there are many paths to activate them into mitosis.
Immune cells can become a cancer just by their number and statistics of error. Just big leukemia is but a symptom but has potential for first stage cancer.
Forgive this (very tortured) analogy, but I think there is a lesson here for would-be extropians who think society will simply tolerate a few vampires here and there.
Specifically: they'd better be living lives of quiet, impoverished contemplation ...
It's randomness. Theoretically speaking every possible combination could happen. So you should be able to have a Cancer cure, a cancer resistant to that, another cure, another cancer, etc.. at least until you cover all of the possibilities.
The goal is to have science become faster than physical mutations. You generate medicines faster than you generate resistant mutations.
How many times in the last 10 years have we gone bananas on HN for an immunotherapy wonder drug just to find it’s another casualty of the current unable-to-reproduce crisis in current science?
Remember when CD47 monoclonal antibodies from the Stanford trials were going to save millions of lives? What a time to be not yet dead that was.
The poster above is correct. Wanting this to be something wonderful doesn’t make it so, and anyone familiar with the subject matter knows this deserves skepticism. This is getting upvoted because it sounds good, not because there’s solid evidence it has legs.
I’d love for this to become a high efficacy treatment for millions of people, but we’ve had the same thing play out so many times now that it’s impossible to be excited.
This is what usually happens:
They’ll try it in the lab, and it’ll kill cancer.
They’ll inject it in mice, and it’ll kill cancer.
They’ll try it on people, and it’ll reduce the size of their tumors for six-to-eight weeks before they start growing again.
I’ll remember to check back in a year to to see if this is even still a thing.
The Emperor of All Maladies is one of my favourite non-fiction books. As long as you can get through the human experimentation. That’s hard going (and horrifying).
> The team says human trials on terminally ill patients could begin as early as November if the new treatment passes further laboratory safety testing.
However, I'd take exception to 'it can only do good'. I've had a loved one opt for experimental treatment that was ineffective, and made the last months of his life more painful and separated from his family (treatment was in another city). I'm not saying we would choose differently if we were faced with it again, but in some respects I wonder if it was more a service to our peace of mind at having done all we could than it was for his comfort or happiness.
He was a spiritual man and didn't seem regret the decision, but his family had a harder time with it. They were arguing for something closer to hospice, and wanted to take him traveling to enjoy the last months of his life in relative peace. In the end, that didn't get to happen.
There will always be a twinge of regret, I think. One can always look back and ask, "what if we had done it this way?" But it was the way he wanted to go, and I think the knowledge that he had tried everything that he could helped him to find peace.
(On the other hand if this was an experiment and it just didn't go his way, that's another story. We need brave people to accept these experimental treatments sometimes to find whether they work.)
We seem to know so little about how our bodies work. There are no bio markers for some of these or early detection and little idea what are the causes or the important details of what's happening as the disease progresses.
Time after time I saw patients pleading with a nurse for more pain relief, and the answer came back, "You can only have so many in a 24 hour period, so you have to wait for another hour before I can give you any more."
The number of people I saw on one small ward who had hours each day full of really bad pain convinced me that pain relief would be one of the best places a philanthropist could spend money. If you're in that much pain you can't think properly, can't enjoy life, and it's all ultimately unnecessary, because, once a doctor and a patient agree there's something wrong and what to do about it, additional long-term suffering doesn't add anything to the experience.
People can have cancer. They can have arthritis. They can have a bad back, or kidney stones, or pancreatitis. I do think all those should be cured if possible. But the one constant misery for so many people, even if someone simply has old age - is pain.
Wait a bit, the next cycle of oversteer will start soon enough.
Not excusing it. Just explaining.
I encourage everyone to figure out what works for them proactively. Because eventually everyone will need it.
 Ideally we should work towards broader / more fundamental goals such as "well-being" and "meaning", but that is even more difficult.
2. Heart disease.
5. Mental health conditions.
7. Nervous system disorders.
10. Developmental disorders.
1. Heart disease.
4. Chronic lower respiratory disease.
8. Influenza and pneumonia.
9. Kidney disease.
Side note: I was surprised to see arthritis at #1 on the DALYs list. Seems like more research is needed here, as well.
To even define and understand the problem properly we have to solve a bunch of things. Then to get to a solution a bunch of other things need to be figured out and can be integrated into humanities knowledge base. On top of that things can be dragged in from other fields to get a sense of how biology responds at various scales: genetic, tissue, organ, system, whole person. It's a perplexing and fascinating disease to grapple with.
For mental health, what's primarily needed is more access to therapy.
Also, this is a commonly misunderstood issue. We are increasingly finding that "psychological" issues have strong links to physiological issues. Here is one example (of many):
Autoimmune disorders can lead to a huge variety of neurological/psychological issues. All work on better understanding of the immune system is going to help many overlapping disorders.
What have previously been seen as "psychological" issues are, for these disorders, only marginally improved by therapy. Therapy can help someone cope, but root causes might be based on immune system issues.
I could of course be wrong, but my own unfounded suspicion is that in a few years we will find that a lot of current mental health therapy was rather stone age. Much may be replaced by more fundamental treatments to eliminate the source of basal ganglia (or other structures) inflammation that led to the psychological disorder.
As far as comparing to cancer, it seems plausible to me that some measurement like "quality adjusted years lost" (or impaired) could show it's more significant than cancer. I hesitate to say we need more research for anything, because unlimited funding leads to garbage research. But good research is needed. One of the most interesting developments in the last couple decades, I think, was "optogenetics" - techniques that allow scientists to manipulate neurons in a living subject by using light. But just funding more research may just mean torturing a few more mice to no purpose.
We need better, more effective, treatment for entrenched eating disorder.
We need better treatments for treatment-resistant depression or anxiety disorders.
Currently most mental health medicine is like throwing darts in the dark. We clearly don't actually understand why some medications work for some people but not others. If you go through the medicine path then I can only wish you the best of luck - finding the right medicine is life changing but it's a long arduous struggle to find it currently.
Not to mention the side effects...
There are plenty of psychoactive drugs where we have no understanding of why they work at all. Lithium is one of the oldest, most successful, and best known medications for bipolar disorder, major depression, and schizophrenia, and we have no idea which of the many effects it has on the body actually contribute to stabilizing mood.
But, we also need better access to addiction treatment (decriminalization would be a huge step here), more drug research, and a huge push to remove the stigma of mental health conditions in general.
The way you identify a serious case is where the forming and/or maintenance of normal relationships is seriously impaired. Therapy is a way of providing needed human contact. It's just not addressing the underlying problem.
That's measurably not true.
The consequences of not working (so long as it's not counterproductive) on an non-severe (so long as not also progressive) case may be less than a severe case, but that doesn't mean that everything works in those cases.
Edit: Further you implied that the purpose of therapy is to provide human contact not just that it involves human contact.
But from a brutally pragmatic point of view, the point holds.
>Nearly all of the evidence linking physical activity to cancer risk comes from observational studies, in which individuals report on their physical activity and are followed for years for diagnoses of cancer. Data from observational studies can give researchers clues about the relationship between physical activity and cancer risk, but such studies cannot definitively establish that being physically inactive causes cancer (or that being physically active protects against cancer). That is because people who are not physically active may differ from active people in ways other than their level of physical activity. These other differences, rather than the differences in physical activity, could explain their different cancer risk. For example, if someone does not feel well, they may not exercise much, and sometimes people do not feel well because they have undiagnosed cancer.
I would really like to see some proper studies done. Unfortunately, seeing friends and otherwise healthy, physically active people passing away from cancer at a relatively young age does not inspire hope at the moment.
In particular, there appears to be a causal link between being fat and an increased risk of some cancers via several identified mechanisms, though of course this whole area is a subject of ongoing research.
Given the well-understood links between a healthy diet, getting enough exercise, and maintaining a healthy body composition, it's important to pay attention to both diet and exercise in order to minimise cancer risk, even taking into account the other effects.
Of course, avoiding obesity is advisable for everyone where possible, for all kinds of reasons.
But there are cases where a complex physiological problems (particularly autoimmune issues) can contribute to obesity and cancer risk.
Such cases are quite possibly more frequent than is generally understood, given how many people try and fail to lose weight through diet and exercise.
Metabolic rates vary significantly, and rates of absorption of nutrients and consumption of energy vary a lot as a result of factors such as inflammation and endocrine function.
Calories in/calories out may still ultimately be true when you boil it down far enough, but the factors influencing and intervening in those processes are vastly complex and strongly affected by diseases and dysfunctions that are very common.
Thyroid disorder (which can include cancer or a precursor condition) is probably the most common/known, but just one of many.
Alzheimer's is a bad example.
There is in fact evidence of success with treatments that treat underlying brain infection rather than preventing amyloid beta plaques from forming. 20 years of barking up the wrong tree may be at an end soon.
[Edit] from 1B to 4B if you count subcategories. Expect good things in the future.
Assuming you mean Huntington’s, there’s a whole bunch of very promising treatments being trialed.
theoretically this could may made into a therapy by taking t cells from patients, modifying their DNA to express this receptor, and then readministering the modified t cells to patients
there are two FDA approved drugs that use this basic approach. however, this only works currently in "liquid tumors", not "solid tumors" like breast cancer, lung cancer, prostate, etc
This article gives a nice, simple explanation as to why solid tumors are more difficult (scroll down to the chart): https://www.the-scientist.com/features/the-next-frontier-of-...
if this works, then the first challenge listed in the chart would be mitigated. however the challenges of a suppressive tumor environment and sufficient delivery to tumor cells is still a major unsolved challenge
> However, the research has been tested only in animals and on cells in the laboratory, and more safety checks would be needed before human trials could start.
> Lucia Mori and Gennaro De Libero, from University of Basel in Switzerland, said the research had "great potential" but was at too early a stage to say it would work in all cancers.
> These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.
So it hasn't come (to the journalists) from nowhere.
> "At the moment, this is very basic research and not close to actual medicines for patients."
> Prof Sewell said the ‘right people’ are now interested in developing the potential new therapy and said progress could now move ‘quite fast’. The team says human trials on terminally ill patients could begin as early as November if the new treatment passes further laboratory safety testing.
Some level of skepticism is certainly warranted, but it's not impossible that this is way closer to "actual medicines for patients" than you might think.
Leaches and amputations without anesthetic were once “state of the art”, and it feels like that’s where we’re currently at with cancer therapies. CRISPR is knocking on the door of amazing potential.
The abstract for the original article notes:
> ... An MR1-restricted T cell clone mediated in vivo regression of leukemia and conferred enhanced survival of NSG mice. TCR transfer to T cells of patients enabled killing of autologous and nonautologous melanoma. ...
What does that second sentence mean?
Here are some the descriptions of the related methods currently researched:
(of cells or tissues) obtained from the same individual.”
And where does this fit into transplant rejection? Perhaps MR-1 differs enough between people to cause problems. This reads like the early days of a discovery that could lead anywhere.
Also, I'm pretty sure there is already an increase in autoimmune disorders after current immuno-oncology (IO) treatment. Patients should certainly have that information before treatment.
Is there some open source scientific community/repository like GitHub? (Where people can pull down the latest data and ideas, and add to them, then push our changes back to the main scientists.)
A repository of ideas from non-experts will probably slow down things rather than help them. I'm not dismissing the idea outright; perhaps there's a way structured inputs from patients and caregivers can be helpful (again with some review mechanism so that real researchers don't have to wade through irrelevant data.)
Most of the people in this thread have about as much reason to "share ideas" with cancer researchers as a 9 year old has to share ideas about your line-of-business form-over-data web application.
What I would like to see is a world in which doctors and researchers ask "Why isn't your body already making enough of these and what can we do to help it crank them out in sufficient quantities?"
These are deaths / 100'000 people. It's a bit difficult to judge precisely in that resolution, but death by cancer is <1%/year before the age of 40. That was roughly the life expectancy (assuming you made it past childhood, big if), for humans during most of their evolution.
So the likely answer is that it never mattered to our body (or survival) to combat cancer effectively.
My understanding is that Paleolithic peoples generally had a life expectancy of about 50-60, assuming that you survived childhood. The development of Neolithic probably lowered life expectancy somewhat (since, basically, people eating an agricultural diet are essentially chronically malnourished until sometime in the Early Modern).
Nowhere have I seen any indication that the life expectancy of humans, at any point in time, was as low as 40.
> Based on Neolithic and Bronze Age data, the total life expectancy at 15 would not exceed 34 years.
Which in turn cites this article: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajpa.1330300...
Either way, your framing has zero bearing on my point. If they can produce them in quantity in vats for purposes of combatting cancer, why not produce them in quantity in the body? That's my point.
I tried to answer "why are these not naturally produced in quantity by your body".
Are you asking why the scientists didn't alter human bodies to artificially produce these cells in quantity inside the body? No idea, but that does sound a lot more difficult/dangerous than producing them in a vat?
"Why isn't your body already making enough of these..
And I don't think it is dangerous to wonder what the hold up is and try to do research to answer that question. But it seems like no one here is actually getting what I'm trying to say.
It's late. I'm tired. Whatevs.
Imagine you need to make Excel export csv documents with dots instead of commas, and there is no easy option to toggle. The app was grown, not designed, so same commas are used in all kinds of other places in the output and in memory and even in the byte code and even in processor cache buffers. Only sane option is to add some post-processing.
That's not really what I'm thinking about though.
Peter Thiel started HGH therapy in 2014 because ,,cancer would be cured in 10 years anyways''.
It seems to me like his prediction is coming true (maybe we'll need 5 extra years though).
This is not just chemo either; immunotherapies can be brutal.
A major question is the cost of the therapy. If it equals CAR-T, which it closely resembles, it will NOT see rapid adoption until the price per treatment falls below CAR-T's current bill of $500,000 US.
That said, with trials there’s a good chance a patient will wind up in the control group (sad trombone), and a lot of new treatments don’t work all that well, or merely extend survival for a few months in exchange for several side effects. A LOT of trials are also simply studying the efficacy of the combination of known treatments; these trials are safer bets, but they’re also unlikely to provide one with a miracle.
With immunotherapies, keep in mind that side effects during treatment can be severe and potentially fatal. Basically, if you have late stage cancer and treatment works, you almost die from the toxic effects of your immune system kicking into overdrive and blowing up all the tumor cells in a few days. There’s a ton of supportive therapy. If a new immunotherapy like the one in TFA showed promise, all the necessary supportive therapy acts as a limiter on rapid scale-up, even with perfect knowledge sharing and patient access.
High dose of NMN are supposed to be helping develop some cancers.
angular chelitis is totally new to me. Are you on retinoids by any chance?
(Although there’s no indication his status led to his cure, of course. With immunotherapy, the requisite status seems to be “can become patient of a decent clinic,” not “former leader of the free world” and/or legendary rock god.)