13 ms·

'Living Drug' That Fights Cancer by Harnessing Immune System Clears Key Hurdle

423 points by daegloe 9y ago

ceejayoz 9y ago
> Another big concern is the cost. While Novartis will not estimate the price it will ultimately put on the treatment, some industry analysts project it will cost $500,000 per infusion. Welp, guess my insurance premiums aren't stabilizing anytime soon.
- seibelj 9y ago
  There won't be that many people who need this drug, and supposedly it's a one-time cure that isn't a life-long drug treatment. I'm a layman when it comes to biotech, but my hope is that longterm the prices come down for this and other drugs that use a similar technique to treat diseases. I'm happy researchers are focusing on cures rather than "living-with" a disease. Also, shoutout to Boston (and Cambridge) which I don't think gets enough love on HN. #1 in the entire world for biotech, #2 for software, #1 for higher ed, #1 for healthcare, you can actually afford to live here, solid public transportation, amazing skiing / hiking / beaches, NYC in 4 hours. If you are tired of SF think about Boston
  - im_down_w_otp 9y ago
    You lost me at "amazing skiing" ;-)
  - rhexs 9y ago
    You can afford to live there? I was looking at 1 br apartments in Cambridge and it was pretty darn close to SF Bay. Interviewers I was talking to said they commuted in 45 minutes just so they could own a house.
    - tomkinstinch 9y ago
      The unspoken assumption is that it's affordable if you have roommates (or a solid dual-income household). I have a place in Providence, RI and commute to Cambridge, MA by train (38 minutes to South Station via Amtrak, double that via MBTA). It's a shorter commute than when I rented in Brookline. Because of all of the Boston-area colleges, students set the standard. The housing stock is higher quality (and lower price) once you escape Boston/Cambridge, where students will live in any sort of derelict apartment, and use loans to pay inflated prices for the privilege. Boston has many things going for it, but the housing market is a real problem. Don't get me started on "broker fees"...
      - nerdponx 9y ago
        it's affordable if you have roommates This is the story in NY too. It definitely does not qualify as "affordable" for anyone with a family.
    - nck4222 9y ago
      >commuted in 45 minutes I live in and work in Boston, and my commute is 45 minutes. I'm planning to move further out to buy a house, and my commute will probably still be roughly 45 minutes. Unless you live within walking distance of your office or feel like you have a safe enough bike route to the office, 45 minutes is a fairly standard commute here.
    - agentgt 9y ago
      I live in Waltham and while I don't work in Boston (work from home) it only takes me 15-25 minutes (depending on where in the city) to get into Boston. The Boston area has awesome suburbs that aren't really suburbs like Newton, Arlington, Waltham, Brighton, Melrose (where incidentally Martin Fowler lives) etc. I know everyone wants to live in the city cause its cool but these mini cities are pretty darn cool as well. From most of these areas you can get into the city in 20 minutes by car. 40 minutes if there is bad traffic. And of course there is public transportation. Compare this to most of the metropolises in America: Atlanta, Dallas, Houston, etc that have massive traffic and suburbs that are truly suburbs (boring as can be).
      - jseliger 9y ago
        Compare this to most of the metropolises in America: Atlanta, Dallas, Houston, etc that have massive traffic and suburbs that are truly suburbs (boring as can be). Yet those boring metropolises have something key: affordable housing. Which is why the world is looking a lot more like them: http://www.newyorker.com/magazine/2017/07/10/americas-future-is-texas http://www.newyorker.com/magazine/2017/07/10/americas-future.... While most MA suburbs prohibit most development, thus causing prices to skyrocket: https://www.bostonglobe.com/business/2017/05/16/somerville-housing-debate-echoes-across-region/HkCa6jijZ8bHGNlCdBVJiN/story.html https://www.bostonglobe.com/business/2017/05/16/somerville-h...
        agentgt 9y ago
        I generally agree but often those affordable houses are massive cheaply made McMansions (particularly in Texas). Living in New England I'm often envious and this is probably coming from jealously but really family's of 5 don't need 6000 square feet, a pool, a 3 car garage, and 2 acres of land. You can always live like the Europeans and most of the rest of the world does and there are condos sub 300,000 in the MA suburbs.
        bluGill 9y ago
        Sure you can, but would you want to? 6000 square feet means I have a place for my hobbies, with the tools all setup so I can do something for 10 minutes if that is all the time I have for them. I like my pool, it is a lot easier to go swimming when the pool is just out your door as opposed to having to go someplace else. I like having room in my garage for my collectable car. I like having my garden close enough that I can get fresh greens on a whim. The point is different life choices enable different lifestyles. I've seen wood workers in Europe produce beautiful things in a tiny apartment. They prove it can be done, but they don't have the space for a table saw and as a result everything they do takes longer. Even if hand tools are the goal, in the large shop you turn around and your saw bench is there, while the European has to get it out of the closet. When done the American sweeps and is done while the European counterpart has to put the bench away as well. When I'm working I want the American style shop. Your choices may be different, that is your choice. Do not try to force other people to like your choice.
  - numbsafari 9y ago
    Funny... Weren't these studies done in Philly, not Boston? And isn't the Novartis lab based out of Switzerland? I missed the part about Boston in this article...
- pinaceae 9y ago
  how much is getting cured of cancer at a very young age worth? dying vs. living another 80-90 years? less than a Tesla? more than a house? interesting questions arise around immuno-oncology. should Apple be the most profitable company - or someone that literally cures cancer?
  - orbitur 9y ago
    > how much is getting cured of cancer at a very young age worth? dying vs. living another 80-90 years? > less than a Tesla? more than a house? It's worth so much that a person shouldn't be required to pay for it. Like a right.
    - deelowe 9y ago
      Whether or not an individual pays for it has nothing to do with the pricing the manufacturer sets. In fact, setting prices becomes even more of a concern when these things are being funded by tax dollars as the government is going to need a way of determining what's reasonable.
      - toomuchtodo 9y ago
        When a manufacturer sets the price, they want to recoup the costs and then make a profit on each unit sold. When a government funds the research, the marginal cost for each unit provided is time and materials, with no profit. Government funds projects every day that are waste, spending tens, even hundreds of millions of dollars. We can continue to pour money down the F-35 drain but not provide healthcare? Make America Intellectually Honest Again
      - jrimbault 9y ago
        Anglo-Saxons (in general, not all, but in particular Americans) are so very weird when it comes to the "free market". IMO (dirty socialist/communist that I am), healthcare is not part of the free market. The industry providing healthcare should be strictly regulated and no benefits allowed. Also, what's worth healthcare compared to the US DOD spending?
- gozur88 9y ago
  This won't affect your insurance - the patient population is too small. Now, if a similar treatment gets approved for, say, prostate cancer... that's going to affect your insurance.
  - zamalek 9y ago
    > the patient population is too small. I think that cancer is one of the great filters. At some point a species will develop an unreliable way to treat cancer (chemotherapy); at which point cancer becomes a genetic problem as natural selection is displaced by medicine. Over many generations, this will kill a species unless a reliable cure is found - we seem to have that cure. Our cure is symptomatic (cancer being the symptom) but the same technology could eventually be used for designer genetics. Essentially, more and more people are going to rely on this treatment until we are able to completely eradicate hereditary cancer. Probably not in our lifetimes.
    - gozur88 9y ago
      But cancer isn't primarily a genetic problem; it's a consequence of the way our bodies work at the cellular level. We all accumulate genetic damage over time from a variety of sources, and we'll all get cancer eventually if something else doesn't kill us first.
      - zamalek 9y ago
        That is the story for most people today but is not the entire story. If your mother had breast cancer then you are at a higher risk - if not for genetics that would be magic. That is why I specifically said "hereditary cancer."
        philjohn 9y ago
        Yep, other hereditary cancer syndromes too, such as Von-Hippel Lindau, which is a mutation in a tumour suppressor gene.
    - bykovich2 9y ago
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eatbitseveryday 9y ago
NYTimes also covers the story (https://www.nytimes.com/2017/07/12/health/fda-novartis-leukemia-gene-medicine.html https://www.nytimes.com/2017/07/12/health/fda-novartis-leuke...) with more discussion about individual patients. From the NYT article: > The panel recommended approving the treatment for B-cell acute lymphoblastic leukemia that has resisted treatment, or relapsed, in children and young adults aged 3 to 25. Why so young?
- skadamou 9y ago
  A couple of things really surprised me about this article. First, I'm sure that there is other evidence the FDA is using to determine whether or not to grant this drug FDA approval but a 63 person drug trial seems like an exceedingly small sample size to work with. Perhaps because this disease is so rare they could not put together a larger trial? Also, it seemed a little bizarre for an FDA panel to receive comments about a decision it is trying to reach from the families of those involved in the drug trial. I suppose there is nothing wrong with that, per se, but shouldn't these types of decisions be reach on the basis of scientific evidence and strive to be devoid of any kind of sentimentality? Either way, it's always excellent to see new cancer treatments on the market, particularly when they are as groundbreaking as this one.
  - gumby 9y ago
    It's an orphan indication which has special rules to promote development. Otherwise, the thinkingngoes, nobody would develop treatments for uncommon diseases.
    - bluGill 9y ago
      The downside of this is a treatment that you can get approved for something rare, but now it is on the market and they can tell doctors it has promise for some common X. Getting approval for treating X would be more expensive because you have to do a larger trial. (you should do a large trial for the rare thing, but since there are not enough people with the rare thing you cannot)
JoeAltmaier 9y ago
From the article: "Scientists use a virus to make the genetic changes in the T cells, raising fears about possible long-term side effects" Is this a real risk? Is 'using a virus' in this way, still risky at all? or is it just the word 'virus' that makes writers put this line in every article about gene therapy? {edit: real risk}
- Sir_Substance 9y ago
  A virus is a machine for replacing DNA in a cell with other DNA. Seems like the right tool for the job.
- gumby 9y ago
  It's a standard tool. In fact a virus is not necessary a living device: there's a DNA delivery wrapper (looks like. Little lunar lander with a big spike coming out) and a payload (DNA). A virus can't reproduce but it can inject its payload into a cell and have the cell's DNA copy/execution capabilities copy the DNA for the virus, making new delivery machines until the cell explodes and emits a cloud of new dlivery agents into the organism. But if you remove the payload and replace it with your own, that payload presumably won't make more viruses
  - eatbitseveryday 9y ago
    > It's a standard tool. In fact a virus is not necessary a living device: there's a DNA delivery wrapper (looks like. Little lunar lander with a big spike coming out) and a payload (DNA). Just a slight correction. Not all viruses look like what you describe. [0] Others, like the HIV, are circular. [1] [0] https://en.wikipedia.org/wiki/Virus#Structure https://en.wikipedia.org/wiki/Virus#Structure [1] https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV
- aabaker99 9y ago
  The virus is inactivated HIV. The risks about long-term side effects pertain more to gene editing than the use of a virus as a delivery mechanism.
sjbase 9y ago
Does anyone know: what are the failure rates like for the gene editing technology being used for this? Thinking like a software engineer, are there transposition errors (GATC --> GTAC) , atomicity issues (GATC --> GA)? Mutations afterward?
- jfarlow 9y ago
  In this particular case the therapy is being applied to cells that have been extracted from a patient. That allows a reasonable error rate where errors can be filtered out, and success verified before the cells are reimplanted. This is a strategically nice intermediate before having to run a therapy on a living organism. The technology in use here is not quite the same kind of 'DNA editing' as is found with tools like CRISPR, but rather a much more therapeutically mature (if technologically blunt) form of viral 'insertion of a block of code'. With respect to actual code fidelity, errors in DNA come from a number of different sources. Every time DNA is copied (a cell divides) there is an inherent fidelity rate of the copy (on the order of a single mistake per billion writes). The payload here is on the order of a few thousand base pairs so copies should have a very high fidelity. In this case a viral protein is 'inserting' its DNA randomly into the genome of the target cells. Imagine inserting a library of code randomly into a codebase. Certainly not ideal, and an issue that CRISPR technologies promise to help improve. However, given that the therapy is only being applied to immune cells that are only running the 'immune' section of the human codebase, and no progeny of those cells will ever have to become a brain or skin or run any of the other programs, the chance that the inserted DNA disrupts the 'immunological' code in the codebase is relatively small. And if there is disruption to some cells' genomes those cells could be screened out if they really distort something they should not. With respect to DNA generally, common errors arise from undesirable but common chemical modifications to the code itself. The DNA can become damaged (by reactive oxygen, UV light, and through other chemical reactions), and while there are significant systems to repair that damage, oftentimes since there is only a single backup (DNA is 'double-stranded'), it's often impossible for that machinery to determine whether the error is on strand1 or strand2, so 50/50 chance of 'repairing' into the error.
stillfinite 9y ago
The significant thing about CAR-T cell therapy is that it's not very specific to the type of cancer - all cancer cells have damaged DNA that leads to the productions of antigens. Leukemia is the low-hanging fruit because it's easy to inject the T-cells back into the body right where the cancers cells are. It's hard to tell whether you could get enough T-cells to diffuse out of the bloodstream to have an effect on something like prostate cancer. It would be a real breakthrough if you could overcome that hurdle, because then you would have a treatment that works on many different cancers without much modification.
- hwillis 9y ago
  Real, actual question: would it not work to just inject t-cells deep into my taint in that case?
  - HillaryBriss 9y ago
    i second that question. if they can carry out needle biopsies of the prostate and other cancer locations, if they can surgically remove cancerous tissue -- why can't they also get these modified cells to the cancerous locations somehow?
  - Cerium 9y ago
    What I got out of the article was that the approach here seems to be that you create a small number of improved t-cells and inject them. Then these improved t-cells will respond correctly upon contact with cancer cells. At that point they will multiply to meet the required demand. The initial injection would be more like a vaccine than a drug.
    - inlined 9y ago
      The t-cells would multiply? I thought they were created in the bone marrow. Do bloodstream t-cells go through meiosis?
  - vibrio 9y ago
    "local' anticancer treatment is achievable but not really effective. the promise in the CAR-T is persistence of the cells and systemic distribution so they can surveil for micro metastases and minimal residual disease, hopefully eliminating it. I'm not sure injecting a ton of cell into ones taint would give the cells the best opportunity to persist and provide systemic prevention.
jfarlow 9y ago
Congratulations! The Chimeric Antigen Receptor (CAR) deployed here is very much unlike the standard 'small molecule' drug that 'disrupts a bad thing', and much more like a rationally engineered tool using the body's very own technologies to overcome a particular limitation. In this case, it gives the patient's own immune system a notion of what the cancer looks like. If you want to build your own 'living drugs' we've built a digital infrastructure to allow you. Though we just made public our generic protein design software (thanks ShowHN! [1]), we're employing the same underlying digital infrastructure to build, evaluate, and manage CAR designs in high throughput [2]. 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. [1] https://news.ycombinator.com/item?id=14446679 https://news.ycombinator.com/item?id=14446679 [2] https://serotiny.bio/notes/applications/car https://serotiny.bio/notes/applications/car Design your own 'living' protein drugs here right now: https://serotiny.bio/pinecone/ https://serotiny.bio/pinecone/ (and let us know what you think, and how we can make it better!)
- skummetmaelk 9y ago
  3...2..1.. Prion disease! Seriously though, how would you prevent such automated designing from having unintended side effects?
  - jfarlow 9y ago
    The software is useful because it allows you to have some idea of the function of each component prior to their assembly. Further, at this point, the software is designed for R&D far far upstream of being put directly used as a therapeutic. Finally, if a design causes some problem, we want to know that - we allow that undesirable property to be discovered in the laboratory, annotated, and communicated so that others know to not use such designs.
    - skummetmaelk 9y ago
      Is it actually possible to construct proteins from functional components like we design digital logic and software? Don't the parts interact in highly complex ways that take a lot of compute time to solve?
aaronbrethorst 9y ago
"While Novartis will not estimate the price it will ultimately put on the treatment, some industry analysts project it will cost $500,000 per infusion." Meanwhile, the latest version of the US Senate's healthcare bill includes the so-called Cruz Amendment[1], which would allow insurance companies to offer health insurance plans without essential health benefits, which would allow lifetime caps on insurance[2], which could mean that your six year old with recurring leukemia gets pulled off their treatment when they're halfway through. Not because you did anything wrong, per se, but because maybe your employer refuses to spring for health care plans with more than an $x dollar cap. Or you never anticipated something so horrific and catastrophic happening to your family. [1] https://www.nytimes.com/2017/07/13/us/politics/senate-republican-health-care-bill.html https://www.nytimes.com/2017/07/13/us/politics/senate-republ... [2] https://www.brookings.edu/2017/05/02/allowing-states-to-define-essential-health-benefits-could-weaken-aca-protections-against-catastrophic-costs-for-people-with-employer-coverage-nationwide/ https://www.brookings.edu/2017/05/02/allowing-states-to-defi...
- logfromblammo 9y ago
  You could always pay the alternate price of kidnapping a Novartis executive's child until the treatment is completed, and then surrendering yourself to a lengthy prison term afterward. I can't pay $500k out of my own pocket, but I can buy a roll of duct tape and rationalize the hell out of an ethically tricky situation. That's one of the classic posers to gauge someone's level of ethical maturity, isn't it? Your child is dying, and you cannot afford the treatment. Would you steal it instead of buying it? Why?
- sloppycee 9y ago
  That sounds horrible. Although, I do wonder what effects there would be if a cancer cure-all were discovered. Since nearly everyone would need the treatment at some point, it wouldn't really be insurance anymore; more like a mortgage.
  - PeterisP 9y ago
    We're already at this stage - we have many life-extending (there's no life saving, only extending it for smaller or larger amounts) treatments and procedures, and the amount is growing. For pretty much every patient who dies currently we could extend their life a bit more (not they'd always want that, mind you) if we put in more resources in that patient. It's tautologically clear that it's not possible to do everything for everyone, i.e. a community 100% composed of doctors and nurses wouldn't be able to provide all the possible life-extending things (especially late in life/close to death) to everyone of themselves. So one way or another we need a process to decide where we stop, i.e. what life-extending things will not be provided to which people. Of course, there's a major practical difference between in a process that takes/costs one day of labor and extends life expectancy by a year, and a process that takes/costs a year of labor and extends life expectancy by a day - but there's no conceptual difference, and we have options all along that scale to find where the tradeoff starts/stops making sense.
Young_God 9y ago
A friend of mine is alive today because he was part of one of the early trials. He had been told by his doctor, just before he was accepted into the trial, that he should start putting his affairs in order.
judah 9y ago
Is this the same CAR-T treatment that Juno Therapeutics tried and scrapped[0] after 5 trial patients died after receiving the treatment? [0]: http://www.xconomy.com/seattle/2017/03/01/after-trial-deaths-juno-pivots-and-scraps-lead-car-t-therapy/ http://www.xconomy.com/seattle/2017/03/01/after-trial-deaths...
- ksenzee 9y ago
  No. From the article: > In the past, a handful of patients who were getting similar treatments developed by other companies died from serious brain swelling. Although those sorts of complications did occur in some patients receiving CTL019, the patients recovered and there were no fatalities, the company says.
known 9y ago
Isn't this how vaccines work?
- jfarlow 9y ago
  Vaccines work by previewing a foreign object, that if seen again, the immune system will attack. The big difference in treating cancer is that there is nothing 'foreign' about cancer - it arises from one's own cells. Cancer is an unproductive or even malicious mashup of material already found in the human body, very much unlike a viral or bacterial infection. There are no natural differences in kind that can be detected by an immune system that would not otherwise attack healthy tissue as well. In this case there is essentially a synthetic sensor designed and provided to the immune system that is precisely tuned in the lab to detect the (very subtle) differences between a cancer cell and a healthy cell.
known 9y ago
it will cost $500,000 per infusion
- dajohnson89 9y ago
  Making the choice between being indebted for your entire life and just dying is surprisingly hard for me.

423 points by daegloe 9y ago

> Another big concern is the cost. While Novartis will not estimate the price it will ultimately put on the treatment, some industry analysts project it will cost $500,000 per infusion. Welp, guess my insurance premiums aren't stabilizing anytime soon.

seibelj 9y ago
There won't be that many people who need this drug, and supposedly it's a one-time cure that isn't a life-long drug treatment. I'm a layman when it comes to biotech, but my hope is that longterm the prices come down for this and other drugs that use a similar technique to treat diseases. I'm happy researchers are focusing on cures rather than "living-with" a disease. Also, shoutout to Boston (and Cambridge) which I don't think gets enough love on HN. #1 in the entire world for biotech, #2 for software, #1 for higher ed, #1 for healthcare, you can actually afford to live here, solid public transportation, amazing skiing / hiking / beaches, NYC in 4 hours. If you are tired of SF think about Boston
- im_down_w_otp 9y ago
  You lost me at "amazing skiing" ;-)
- rhexs 9y ago
  You can afford to live there? I was looking at 1 br apartments in Cambridge and it was pretty darn close to SF Bay. Interviewers I was talking to said they commuted in 45 minutes just so they could own a house.
  - tomkinstinch 9y ago
    The unspoken assumption is that it's affordable if you have roommates (or a solid dual-income household). I have a place in Providence, RI and commute to Cambridge, MA by train (38 minutes to South Station via Amtrak, double that via MBTA). It's a shorter commute than when I rented in Brookline. Because of all of the Boston-area colleges, students set the standard. The housing stock is higher quality (and lower price) once you escape Boston/Cambridge, where students will live in any sort of derelict apartment, and use loans to pay inflated prices for the privilege. Boston has many things going for it, but the housing market is a real problem. Don't get me started on "broker fees"...
    - nerdponx 9y ago
      it's affordable if you have roommates This is the story in NY too. It definitely does not qualify as "affordable" for anyone with a family.
  - nck4222 9y ago
    >commuted in 45 minutes I live in and work in Boston, and my commute is 45 minutes. I'm planning to move further out to buy a house, and my commute will probably still be roughly 45 minutes. Unless you live within walking distance of your office or feel like you have a safe enough bike route to the office, 45 minutes is a fairly standard commute here.
  - agentgt 9y ago
    I live in Waltham and while I don't work in Boston (work from home) it only takes me 15-25 minutes (depending on where in the city) to get into Boston. The Boston area has awesome suburbs that aren't really suburbs like Newton, Arlington, Waltham, Brighton, Melrose (where incidentally Martin Fowler lives) etc. I know everyone wants to live in the city cause its cool but these mini cities are pretty darn cool as well. From most of these areas you can get into the city in 20 minutes by car. 40 minutes if there is bad traffic. And of course there is public transportation. Compare this to most of the metropolises in America: Atlanta, Dallas, Houston, etc that have massive traffic and suburbs that are truly suburbs (boring as can be).
    - jseliger 9y ago
      Compare this to most of the metropolises in America: Atlanta, Dallas, Houston, etc that have massive traffic and suburbs that are truly suburbs (boring as can be). Yet those boring metropolises have something key: affordable housing. Which is why the world is looking a lot more like them: http://www.newyorker.com/magazine/2017/07/10/americas-future-is-texas http://www.newyorker.com/magazine/2017/07/10/americas-future.... While most MA suburbs prohibit most development, thus causing prices to skyrocket: https://www.bostonglobe.com/business/2017/05/16/somerville-housing-debate-echoes-across-region/HkCa6jijZ8bHGNlCdBVJiN/story.html https://www.bostonglobe.com/business/2017/05/16/somerville-h...
      - agentgt 9y ago
        I generally agree but often those affordable houses are massive cheaply made McMansions (particularly in Texas). Living in New England I'm often envious and this is probably coming from jealously but really family's of 5 don't need 6000 square feet, a pool, a 3 car garage, and 2 acres of land. You can always live like the Europeans and most of the rest of the world does and there are condos sub 300,000 in the MA suburbs.
        bluGill 9y ago
        Sure you can, but would you want to? 6000 square feet means I have a place for my hobbies, with the tools all setup so I can do something for 10 minutes if that is all the time I have for them. I like my pool, it is a lot easier to go swimming when the pool is just out your door as opposed to having to go someplace else. I like having room in my garage for my collectable car. I like having my garden close enough that I can get fresh greens on a whim. The point is different life choices enable different lifestyles. I've seen wood workers in Europe produce beautiful things in a tiny apartment. They prove it can be done, but they don't have the space for a table saw and as a result everything they do takes longer. Even if hand tools are the goal, in the large shop you turn around and your saw bench is there, while the European has to get it out of the closet. When done the American sweeps and is done while the European counterpart has to put the bench away as well. When I'm working I want the American style shop. Your choices may be different, that is your choice. Do not try to force other people to like your choice.
- numbsafari 9y ago
  Funny... Weren't these studies done in Philly, not Boston? And isn't the Novartis lab based out of Switzerland? I missed the part about Boston in this article...
pinaceae 9y ago
how much is getting cured of cancer at a very young age worth? dying vs. living another 80-90 years? less than a Tesla? more than a house? interesting questions arise around immuno-oncology. should Apple be the most profitable company - or someone that literally cures cancer?
- orbitur 9y ago
  > how much is getting cured of cancer at a very young age worth? dying vs. living another 80-90 years? > less than a Tesla? more than a house? It's worth so much that a person shouldn't be required to pay for it. Like a right.
  - deelowe 9y ago
    Whether or not an individual pays for it has nothing to do with the pricing the manufacturer sets. In fact, setting prices becomes even more of a concern when these things are being funded by tax dollars as the government is going to need a way of determining what's reasonable.
    - toomuchtodo 9y ago
      When a manufacturer sets the price, they want to recoup the costs and then make a profit on each unit sold. When a government funds the research, the marginal cost for each unit provided is time and materials, with no profit. Government funds projects every day that are waste, spending tens, even hundreds of millions of dollars. We can continue to pour money down the F-35 drain but not provide healthcare? Make America Intellectually Honest Again
    - jrimbault 9y ago
      Anglo-Saxons (in general, not all, but in particular Americans) are so very weird when it comes to the "free market". IMO (dirty socialist/communist that I am), healthcare is not part of the free market. The industry providing healthcare should be strictly regulated and no benefits allowed. Also, what's worth healthcare compared to the US DOD spending?
gozur88 9y ago
This won't affect your insurance - the patient population is too small. Now, if a similar treatment gets approved for, say, prostate cancer... that's going to affect your insurance.
- zamalek 9y ago
  > the patient population is too small. I think that cancer is one of the great filters. At some point a species will develop an unreliable way to treat cancer (chemotherapy); at which point cancer becomes a genetic problem as natural selection is displaced by medicine. Over many generations, this will kill a species unless a reliable cure is found - we seem to have that cure. Our cure is symptomatic (cancer being the symptom) but the same technology could eventually be used for designer genetics. Essentially, more and more people are going to rely on this treatment until we are able to completely eradicate hereditary cancer. Probably not in our lifetimes.
  - gozur88 9y ago
    But cancer isn't primarily a genetic problem; it's a consequence of the way our bodies work at the cellular level. We all accumulate genetic damage over time from a variety of sources, and we'll all get cancer eventually if something else doesn't kill us first.
    - zamalek 9y ago
      That is the story for most people today but is not the entire story. If your mother had breast cancer then you are at a higher risk - if not for genetics that would be magic. That is why I specifically said "hereditary cancer."
      - philjohn 9y ago
        Yep, other hereditary cancer syndromes too, such as Von-Hippel Lindau, which is a mutation in a tumour suppressor gene.
  - bykovich2 9y ago

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eatbitseveryday 9y ago

NYTimes also covers the story (https://www.nytimes.com/2017/07/12/health/fda-novartis-leukemia-gene-medicine.html https://www.nytimes.com/2017/07/12/health/fda-novartis-leuke...) with more discussion about individual patients. From the NYT article: > The panel recommended approving the treatment for B-cell acute lymphoblastic leukemia that has resisted treatment, or relapsed, in children and young adults aged 3 to 25. Why so young?

skadamou 9y ago
A couple of things really surprised me about this article. First, I'm sure that there is other evidence the FDA is using to determine whether or not to grant this drug FDA approval but a 63 person drug trial seems like an exceedingly small sample size to work with. Perhaps because this disease is so rare they could not put together a larger trial? Also, it seemed a little bizarre for an FDA panel to receive comments about a decision it is trying to reach from the families of those involved in the drug trial. I suppose there is nothing wrong with that, per se, but shouldn't these types of decisions be reach on the basis of scientific evidence and strive to be devoid of any kind of sentimentality? Either way, it's always excellent to see new cancer treatments on the market, particularly when they are as groundbreaking as this one.
- gumby 9y ago
  It's an orphan indication which has special rules to promote development. Otherwise, the thinkingngoes, nobody would develop treatments for uncommon diseases.
  - bluGill 9y ago
    The downside of this is a treatment that you can get approved for something rare, but now it is on the market and they can tell doctors it has promise for some common X. Getting approval for treating X would be more expensive because you have to do a larger trial. (you should do a large trial for the rare thing, but since there are not enough people with the rare thing you cannot)

JoeAltmaier 9y ago

From the article: "Scientists use a virus to make the genetic changes in the T cells, raising fears about possible long-term side effects" Is this a real risk? Is 'using a virus' in this way, still risky at all? or is it just the word 'virus' that makes writers put this line in every article about gene therapy? {edit: real risk}

Sir_Substance 9y ago
A virus is a machine for replacing DNA in a cell with other DNA. Seems like the right tool for the job.
gumby 9y ago
It's a standard tool. In fact a virus is not necessary a living device: there's a DNA delivery wrapper (looks like. Little lunar lander with a big spike coming out) and a payload (DNA). A virus can't reproduce but it can inject its payload into a cell and have the cell's DNA copy/execution capabilities copy the DNA for the virus, making new delivery machines until the cell explodes and emits a cloud of new dlivery agents into the organism. But if you remove the payload and replace it with your own, that payload presumably won't make more viruses
- eatbitseveryday 9y ago
  > It's a standard tool. In fact a virus is not necessary a living device: there's a DNA delivery wrapper (looks like. Little lunar lander with a big spike coming out) and a payload (DNA). Just a slight correction. Not all viruses look like what you describe. [0] Others, like the HIV, are circular. [1] [0] https://en.wikipedia.org/wiki/Virus#Structure https://en.wikipedia.org/wiki/Virus#Structure [1] https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV
aabaker99 9y ago
The virus is inactivated HIV. The risks about long-term side effects pertain more to gene editing than the use of a virus as a delivery mechanism.

sjbase 9y ago

Does anyone know: what are the failure rates like for the gene editing technology being used for this? Thinking like a software engineer, are there transposition errors (GATC --> GTAC) , atomicity issues (GATC --> GA)? Mutations afterward?

jfarlow 9y ago
In this particular case the therapy is being applied to cells that have been extracted from a patient. That allows a reasonable error rate where errors can be filtered out, and success verified before the cells are reimplanted. This is a strategically nice intermediate before having to run a therapy on a living organism. The technology in use here is not quite the same kind of 'DNA editing' as is found with tools like CRISPR, but rather a much more therapeutically mature (if technologically blunt) form of viral 'insertion of a block of code'. With respect to actual code fidelity, errors in DNA come from a number of different sources. Every time DNA is copied (a cell divides) there is an inherent fidelity rate of the copy (on the order of a single mistake per billion writes). The payload here is on the order of a few thousand base pairs so copies should have a very high fidelity. In this case a viral protein is 'inserting' its DNA randomly into the genome of the target cells. Imagine inserting a library of code randomly into a codebase. Certainly not ideal, and an issue that CRISPR technologies promise to help improve. However, given that the therapy is only being applied to immune cells that are only running the 'immune' section of the human codebase, and no progeny of those cells will ever have to become a brain or skin or run any of the other programs, the chance that the inserted DNA disrupts the 'immunological' code in the codebase is relatively small. And if there is disruption to some cells' genomes those cells could be screened out if they really distort something they should not. With respect to DNA generally, common errors arise from undesirable but common chemical modifications to the code itself. The DNA can become damaged (by reactive oxygen, UV light, and through other chemical reactions), and while there are significant systems to repair that damage, oftentimes since there is only a single backup (DNA is 'double-stranded'), it's often impossible for that machinery to determine whether the error is on strand1 or strand2, so 50/50 chance of 'repairing' into the error.

stillfinite 9y ago

The significant thing about CAR-T cell therapy is that it's not very specific to the type of cancer - all cancer cells have damaged DNA that leads to the productions of antigens. Leukemia is the low-hanging fruit because it's easy to inject the T-cells back into the body right where the cancers cells are. It's hard to tell whether you could get enough T-cells to diffuse out of the bloodstream to have an effect on something like prostate cancer. It would be a real breakthrough if you could overcome that hurdle, because then you would have a treatment that works on many different cancers without much modification.

hwillis 9y ago
Real, actual question: would it not work to just inject t-cells deep into my taint in that case?
- HillaryBriss 9y ago
  i second that question. if they can carry out needle biopsies of the prostate and other cancer locations, if they can surgically remove cancerous tissue -- why can't they also get these modified cells to the cancerous locations somehow?
- Cerium 9y ago
  What I got out of the article was that the approach here seems to be that you create a small number of improved t-cells and inject them. Then these improved t-cells will respond correctly upon contact with cancer cells. At that point they will multiply to meet the required demand. The initial injection would be more like a vaccine than a drug.
  - inlined 9y ago
    The t-cells would multiply? I thought they were created in the bone marrow. Do bloodstream t-cells go through meiosis?
- vibrio 9y ago
  "local' anticancer treatment is achievable but not really effective. the promise in the CAR-T is persistence of the cells and systemic distribution so they can surveil for micro metastases and minimal residual disease, hopefully eliminating it. I'm not sure injecting a ton of cell into ones taint would give the cells the best opportunity to persist and provide systemic prevention.

jfarlow 9y ago

Congratulations! The Chimeric Antigen Receptor (CAR) deployed here is very much unlike the standard 'small molecule' drug that 'disrupts a bad thing', and much more like a rationally engineered tool using the body's very own technologies to overcome a particular limitation. In this case, it gives the patient's own immune system a notion of what the cancer looks like. If you want to build your own 'living drugs' we've built a digital infrastructure to allow you. Though we just made public our generic protein design software (thanks ShowHN! [1]), we're employing the same underlying digital infrastructure to build, evaluate, and manage CAR designs in high throughput [2]. 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. [1] https://news.ycombinator.com/item?id=14446679 https://news.ycombinator.com/item?id=14446679 [2] https://serotiny.bio/notes/applications/car https://serotiny.bio/notes/applications/car Design your own 'living' protein drugs here right now: https://serotiny.bio/pinecone/ https://serotiny.bio/pinecone/ (and let us know what you think, and how we can make it better!)

skummetmaelk 9y ago
3...2..1.. Prion disease! Seriously though, how would you prevent such automated designing from having unintended side effects?
- jfarlow 9y ago
  The software is useful because it allows you to have some idea of the function of each component prior to their assembly. Further, at this point, the software is designed for R&D far far upstream of being put directly used as a therapeutic. Finally, if a design causes some problem, we want to know that - we allow that undesirable property to be discovered in the laboratory, annotated, and communicated so that others know to not use such designs.
  - skummetmaelk 9y ago
    Is it actually possible to construct proteins from functional components like we design digital logic and software? Don't the parts interact in highly complex ways that take a lot of compute time to solve?

aaronbrethorst 9y ago

"While Novartis will not estimate the price it will ultimately put on the treatment, some industry analysts project it will cost $500,000 per infusion." Meanwhile, the latest version of the US Senate's healthcare bill includes the so-called Cruz Amendment[1], which would allow insurance companies to offer health insurance plans without essential health benefits, which would allow lifetime caps on insurance[2], which could mean that your six year old with recurring leukemia gets pulled off their treatment when they're halfway through. Not because you did anything wrong, per se, but because maybe your employer refuses to spring for health care plans with more than an $x dollar cap. Or you never anticipated something so horrific and catastrophic happening to your family. [1] https://www.nytimes.com/2017/07/13/us/politics/senate-republican-health-care-bill.html https://www.nytimes.com/2017/07/13/us/politics/senate-republ... [2] https://www.brookings.edu/2017/05/02/allowing-states-to-define-essential-health-benefits-could-weaken-aca-protections-against-catastrophic-costs-for-people-with-employer-coverage-nationwide/ https://www.brookings.edu/2017/05/02/allowing-states-to-defi...

logfromblammo 9y ago
You could always pay the alternate price of kidnapping a Novartis executive's child until the treatment is completed, and then surrendering yourself to a lengthy prison term afterward. I can't pay $500k out of my own pocket, but I can buy a roll of duct tape and rationalize the hell out of an ethically tricky situation. That's one of the classic posers to gauge someone's level of ethical maturity, isn't it? Your child is dying, and you cannot afford the treatment. Would you steal it instead of buying it? Why?
sloppycee 9y ago
That sounds horrible. Although, I do wonder what effects there would be if a cancer cure-all were discovered. Since nearly everyone would need the treatment at some point, it wouldn't really be insurance anymore; more like a mortgage.
- PeterisP 9y ago
  We're already at this stage - we have many life-extending (there's no life saving, only extending it for smaller or larger amounts) treatments and procedures, and the amount is growing. For pretty much every patient who dies currently we could extend their life a bit more (not they'd always want that, mind you) if we put in more resources in that patient. It's tautologically clear that it's not possible to do everything for everyone, i.e. a community 100% composed of doctors and nurses wouldn't be able to provide all the possible life-extending things (especially late in life/close to death) to everyone of themselves. So one way or another we need a process to decide where we stop, i.e. what life-extending things will not be provided to which people. Of course, there's a major practical difference between in a process that takes/costs one day of labor and extends life expectancy by a year, and a process that takes/costs a year of labor and extends life expectancy by a day - but there's no conceptual difference, and we have options all along that scale to find where the tradeoff starts/stops making sense.

Young_God 9y ago

A friend of mine is alive today because he was part of one of the early trials. He had been told by his doctor, just before he was accepted into the trial, that he should start putting his affairs in order.

judah 9y ago

Is this the same CAR-T treatment that Juno Therapeutics tried and scrapped[0] after 5 trial patients died after receiving the treatment? [0]: http://www.xconomy.com/seattle/2017/03/01/after-trial-deaths-juno-pivots-and-scraps-lead-car-t-therapy/ http://www.xconomy.com/seattle/2017/03/01/after-trial-deaths...

ksenzee 9y ago
No. From the article: > In the past, a handful of patients who were getting similar treatments developed by other companies died from serious brain swelling. Although those sorts of complications did occur in some patients receiving CTL019, the patients recovered and there were no fatalities, the company says.

known 9y ago

Isn't this how vaccines work?

jfarlow 9y ago
Vaccines work by previewing a foreign object, that if seen again, the immune system will attack. The big difference in treating cancer is that there is nothing 'foreign' about cancer - it arises from one's own cells. Cancer is an unproductive or even malicious mashup of material already found in the human body, very much unlike a viral or bacterial infection. There are no natural differences in kind that can be detected by an immune system that would not otherwise attack healthy tissue as well. In this case there is essentially a synthetic sensor designed and provided to the immune system that is precisely tuned in the lab to detect the (very subtle) differences between a cancer cell and a healthy cell.

known 9y ago

it will cost $500,000 per infusion

dajohnson89 9y ago
Making the choice between being indebted for your entire life and just dying is surprisingly hard for me.