9 ms·

'Living drug' offers hope to terminal blood cancer patients

sapilla 7y ago
This reads like the prelude to 90% of all zombie movies - cheating death by injecting virusses, starting in the UK. It even includes a fever and neurotoxicity as side effects.
- ImaCake 7y ago
  They also use a HIV like virus as the vector to modify the T-Cells in the first place!
  - isp 7y ago
    Relevant xkcd: https://xkcd.com/938/ https://xkcd.com/938/
- trampypizza 7y ago
  I thought it sounded a bit like one of the Witcher trials.
- WalterBright 7y ago
  I wouldn't worry about zombies. They violate conservation of energy laws, for one.
  - cdmckay 7y ago
    Also, how do they move if their muscles have rotted away and they have no functioning circulatory system?
    - WalterBright 7y ago
      Yup. Turns out, the organs in the body have a purpose, and without them the body can't work :-) I.e. zombies are magical creatures, even less plausible than godzilla. I also curmudgeonly think that Game of Thrones lost its appeal when it stopped being about political intrigue and became yet another silly magical zombie movie.
      - DennisP 7y ago
        Zombies aren't the only magic in Game of Thrones. They're fantasy novels. If it weren't for the zombies, the political story would just be about people fighting each other for advantage. The zombies add a tension between that and a common cause, since the threat faces them all; much like the world we live in today.
        SketchySeaBeast 7y ago
        I'm guessing they didn't stick around for the dragons.
        WalterBright 7y ago
        The political intrigue was interesting. The zombie apocalypse was a singular lack of imagination - how many zombie movies has Hollywood produced? 200? 300? There are even multiple miniseries about zombies. There's simply nothing interesting about them. Even Lord of the Rings just had to bring in a zombie army at the end, but fortunately didn't spend much screen time on it. The only one I like was the Jason and the Argonauts one where the hero fights a group of skeletons. The herky-jerky Harry Harrison animation is a pleasure to watch. And it was original.
        DennisP 7y ago
        The "zombie army" in Lord of the Rings was in the book Return of the King, published in 1955. The first big, modern zombie movie was Night of the Living Dead in 1968. So I don't think you can blame them for being unoriginal. Also I'd say they were more ghost than zombie, in both book and movie: https://www.youtube.com/watch?v=vYEvmnTghPk https://www.youtube.com/watch?v=vYEvmnTghPk (As for GoT, how many movies have had dragons?)
      - SketchySeaBeast 7y ago
        > I also curmudgeonly think that Game of Thrones lost its appeal when it stopped being about political intrigue and became yet another silly magical zombie movie. So the very first scene of both the books and tv show?
  - deleted 7y ago
    [deleted]
  - dhimes 7y ago
    They violate conservation of energy laws Now I'm even more worried! How can the do that?
    - kennyloginNTH 7y ago
      Big oil killing zombie legalization
  - sapilla 7y ago
    Where do zombies violate conservation of energy? They do wear down eventually, and fresh brains are low entropy and also nutrient dense.
    - WalterBright 7y ago
      They never starve to death, or even weaken. They're not impaired by not having a stomach or a circulatory system to provide energy. The dullards who fight them never think of putting them in a hamster wheel and generating perpetual electric power. Besides, the zombie armies never seem to have any logistics to keep them supplied with brains, or any support logistics at all. There's a reason why predators never evolved armies. (Ok, army ants are predators. But they evolved logistics!)
- dannykwells 7y ago
  Not starting in the UK. These therapies were invented and first approved in the US (CAR-T was invented at Penn and MSKCC)
gaspoweredcat 7y ago
kind of a good and bad thing to call it really though, obviously even though they are dying no one wants a "Dying drug" but likewise "Living Drug" seems to offer a little too much, "Anti-Dying Drug" maybe? :P
- tialaramex 7y ago
  It's a living drug because it's a drug which is in some sense alive. It's made up of T-cells, from the patient's body, but modified. We also distinguish "live vaccine" from "inactivated" or "killed" vaccines, for example OPV the cheapest way to prevent polio is a live vaccine, it's a version of the Polio virus that has adapted to a slow life in a cold medium, and then you eat it (literally, it was traditionally given by adding one drop to a sugar cube, the patient eats the sugar cube, delicious) and your gut goes "What? This is alien - kill it" and you become immune to Polio before it spins back up and causes any harm. Live vaccines are dangerous (which is why we don't use OPV in countries with no polio and plenty of money, even though it is more effective than any alternative) and no doubt this drug is also dangerous, but hey, it's for people with a terminal disease so what's the worst that could happen?
NotSammyHagar 7y ago
This is the way it will work in the future, so many diseases will one by one get treatments that are individualized genetic treatments. They will gradually get cheaper. You will hope to survive till a treatment for your problems get cheap.
- lifeisstillgood 7y ago
  Thank you
ImaCake 7y ago
When I first heard about this I thought it would be another failed wonderdrug. But I am very excited to see it's adoption in mainstream medicine, even if for just the most extreme patients. Treatments like this, and other less audacious immunotherapies give me a lot of hope for the future of decreasing human suffering.
milofeynman 7y ago
They don't mention it in the article but I believe this is the first big treatment to use CRISPR/Cas9 https://www.ncbi.nlm.nih.gov/m/pubmed/30261221/ https://www.ncbi.nlm.nih.gov/m/pubmed/30261221/
- dannykwells 7y ago
  This is not true. The treatment they are getting uses a lentivirus transduced T-cell. CRISPR will eventually be used but in the approved products, not yet.
  - milofeynman 7y ago
    Oh I see, sorry about the confusion.
sslayer 7y ago
So gene therapy with extra steps.
apathy 7y ago
Not mentioned here: the same results can in many cases be had from BiTEs at lower cost and without having to ship leukapheresis samples to the US in liquid nitrogen Having seen both ALL and AML patients relapsing through CAR-T, I don’t think people appreciate either the systemic load or the possibility of treatment failure that exists in real patient populations. Neither was elderly; 26yo female ALL and 5yo female AML. Both dead, both crushing disappointments after the initial excitement. (For CAR-T therapy, the common remark is “you know it’s working when the patient goes to the ICU” from tumor lysis; but in both cases the patient’s disease outran their engineered T cells)
- dannykwells 7y ago
  It's not really fair to compare BiTEs to first gen CAR. Bispecific (or tri/quad specific) CAR have a greatly reduced rate of relapse due to antigen loss (likely what is causing most relapse in these diseases). Re: BiTEs, it's not clear they'll produce durable cures like CAR does. They're just antibodies, and will eventually be cleared. With CAR, if you can get a response, you can generate memory T-cells and control any relapse far down the road.
  - lliamander 7y ago
    Immunotherapy is really fascinating, I know someone going through it right now and it seems to be helping (early days yet, of course). I was very curious to read that it had such severe side-effects, especially the neurotoxicity. Why such a severe reaction? Does the neurotoxicity have developmental impacts for children that receive immunotherapy?
    - dannykwells 7y ago
      The origin of CNS toxicity is still a topic of research. I believe it can occur in children as well (I am not an MD and specialize more in the checkpoint inhibitor side of things).
  - apathy 7y ago
    At least for lineage switching malignancies (5yo female was MLLr), I’m not sure anything other than synthetic lethal attacks on the clonal driver will help. MLL rearrangements in young children have a particularly vile habit of swapping cell surface markers wholesale. They’re almost certainly more potent when they transform fetal liver progenitors, which seem to retain maximum plasticity. AA died prior to the introduction of second and third generation CAR-T, but stan riddell was part of her attending team, so I have to assume all the stops were pulled out. MG was different, 26yo Philadelphia-like ALL with 300k WBC refractory to everything. She should have been on ruxolitinib then transplanted. Her disease simply outran her T cells’ ability to divide. It was unreal. And she was a single mom. I will never forget either case. Even as just an “attached” fellow, it’s hard to watch. More so (for me at least) than older patients where you can reasonably guess what’s coming next. It just feels so unjust. Anyways. Let’s hope I’m wrong and 2nd/3rd gen auto and allow CAR-T can put these kinds of cases into durable remission for the rest of their, hopefully long and healthy, lives. Because right now, nothing does.
GeekyBear 7y ago
Vice on HBO did an episode back in 2015 looking at several different experimental (at the time) cancer treatments which included a segment on the fourth patient to receive CAR-T. https://www.youtube.com/watch?v=FlK-PeCfezM https://www.youtube.com/watch?v=FlK-PeCfezM The CAR-T segment starts at 27:30.
Circuits 7y ago
If cancer was a dude I would punch him in face.
aiyodev 7y ago
> They are frozen in liquid nitrogen and sent to laboratories in the United States. Why do you need to send your blood to an “inferior” healthcare system?

This reads like the prelude to 90% of all zombie movies - cheating death by injecting virusses, starting in the UK. It even includes a fever and neurotoxicity as side effects.

ImaCake 7y ago
They also use a HIV like virus as the vector to modify the T-Cells in the first place!
- isp 7y ago
  Relevant xkcd: https://xkcd.com/938/ https://xkcd.com/938/
trampypizza 7y ago
I thought it sounded a bit like one of the Witcher trials.
WalterBright 7y ago
I wouldn't worry about zombies. They violate conservation of energy laws, for one.
- cdmckay 7y ago
  Also, how do they move if their muscles have rotted away and they have no functioning circulatory system?
  - WalterBright 7y ago
    Yup. Turns out, the organs in the body have a purpose, and without them the body can't work :-) I.e. zombies are magical creatures, even less plausible than godzilla. I also curmudgeonly think that Game of Thrones lost its appeal when it stopped being about political intrigue and became yet another silly magical zombie movie.
    - DennisP 7y ago
      Zombies aren't the only magic in Game of Thrones. They're fantasy novels. If it weren't for the zombies, the political story would just be about people fighting each other for advantage. The zombies add a tension between that and a common cause, since the threat faces them all; much like the world we live in today.
      - SketchySeaBeast 7y ago
        I'm guessing they didn't stick around for the dragons.
      - WalterBright 7y ago
        The political intrigue was interesting. The zombie apocalypse was a singular lack of imagination - how many zombie movies has Hollywood produced? 200? 300? There are even multiple miniseries about zombies. There's simply nothing interesting about them. Even Lord of the Rings just had to bring in a zombie army at the end, but fortunately didn't spend much screen time on it. The only one I like was the Jason and the Argonauts one where the hero fights a group of skeletons. The herky-jerky Harry Harrison animation is a pleasure to watch. And it was original.
        DennisP 7y ago
        The "zombie army" in Lord of the Rings was in the book Return of the King, published in 1955. The first big, modern zombie movie was Night of the Living Dead in 1968. So I don't think you can blame them for being unoriginal. Also I'd say they were more ghost than zombie, in both book and movie: https://www.youtube.com/watch?v=vYEvmnTghPk https://www.youtube.com/watch?v=vYEvmnTghPk (As for GoT, how many movies have had dragons?)
    - SketchySeaBeast 7y ago
      > I also curmudgeonly think that Game of Thrones lost its appeal when it stopped being about political intrigue and became yet another silly magical zombie movie. So the very first scene of both the books and tv show?
- deleted 7y ago
  [deleted]
- dhimes 7y ago
  They violate conservation of energy laws Now I'm even more worried! How can the do that?
  - kennyloginNTH 7y ago
    Big oil killing zombie legalization
- sapilla 7y ago
  Where do zombies violate conservation of energy? They do wear down eventually, and fresh brains are low entropy and also nutrient dense.
  - WalterBright 7y ago
    They never starve to death, or even weaken. They're not impaired by not having a stomach or a circulatory system to provide energy. The dullards who fight them never think of putting them in a hamster wheel and generating perpetual electric power. Besides, the zombie armies never seem to have any logistics to keep them supplied with brains, or any support logistics at all. There's a reason why predators never evolved armies. (Ok, army ants are predators. But they evolved logistics!)
dannykwells 7y ago
Not starting in the UK. These therapies were invented and first approved in the US (CAR-T was invented at Penn and MSKCC)

gaspoweredcat 7y ago

kind of a good and bad thing to call it really though, obviously even though they are dying no one wants a "Dying drug" but likewise "Living Drug" seems to offer a little too much, "Anti-Dying Drug" maybe? :P

tialaramex 7y ago
It's a living drug because it's a drug which is in some sense alive. It's made up of T-cells, from the patient's body, but modified. We also distinguish "live vaccine" from "inactivated" or "killed" vaccines, for example OPV the cheapest way to prevent polio is a live vaccine, it's a version of the Polio virus that has adapted to a slow life in a cold medium, and then you eat it (literally, it was traditionally given by adding one drop to a sugar cube, the patient eats the sugar cube, delicious) and your gut goes "What? This is alien - kill it" and you become immune to Polio before it spins back up and causes any harm. Live vaccines are dangerous (which is why we don't use OPV in countries with no polio and plenty of money, even though it is more effective than any alternative) and no doubt this drug is also dangerous, but hey, it's for people with a terminal disease so what's the worst that could happen?

NotSammyHagar 7y ago

This is the way it will work in the future, so many diseases will one by one get treatments that are individualized genetic treatments. They will gradually get cheaper. You will hope to survive till a treatment for your problems get cheap.

lifeisstillgood 7y ago
Thank you

ImaCake 7y ago

When I first heard about this I thought it would be another failed wonderdrug. But I am very excited to see it's adoption in mainstream medicine, even if for just the most extreme patients. Treatments like this, and other less audacious immunotherapies give me a lot of hope for the future of decreasing human suffering.

milofeynman 7y ago

They don't mention it in the article but I believe this is the first big treatment to use CRISPR/Cas9 https://www.ncbi.nlm.nih.gov/m/pubmed/30261221/ https://www.ncbi.nlm.nih.gov/m/pubmed/30261221/

dannykwells 7y ago
This is not true. The treatment they are getting uses a lentivirus transduced T-cell. CRISPR will eventually be used but in the approved products, not yet.
- milofeynman 7y ago
  Oh I see, sorry about the confusion.

sslayer 7y ago

So gene therapy with extra steps.

apathy 7y ago

Not mentioned here: the same results can in many cases be had from BiTEs at lower cost and without having to ship leukapheresis samples to the US in liquid nitrogen Having seen both ALL and AML patients relapsing through CAR-T, I don’t think people appreciate either the systemic load or the possibility of treatment failure that exists in real patient populations. Neither was elderly; 26yo female ALL and 5yo female AML. Both dead, both crushing disappointments after the initial excitement. (For CAR-T therapy, the common remark is “you know it’s working when the patient goes to the ICU” from tumor lysis; but in both cases the patient’s disease outran their engineered T cells)

dannykwells 7y ago
It's not really fair to compare BiTEs to first gen CAR. Bispecific (or tri/quad specific) CAR have a greatly reduced rate of relapse due to antigen loss (likely what is causing most relapse in these diseases). Re: BiTEs, it's not clear they'll produce durable cures like CAR does. They're just antibodies, and will eventually be cleared. With CAR, if you can get a response, you can generate memory T-cells and control any relapse far down the road.
- lliamander 7y ago
  Immunotherapy is really fascinating, I know someone going through it right now and it seems to be helping (early days yet, of course). I was very curious to read that it had such severe side-effects, especially the neurotoxicity. Why such a severe reaction? Does the neurotoxicity have developmental impacts for children that receive immunotherapy?
  - dannykwells 7y ago
    The origin of CNS toxicity is still a topic of research. I believe it can occur in children as well (I am not an MD and specialize more in the checkpoint inhibitor side of things).
- apathy 7y ago
  At least for lineage switching malignancies (5yo female was MLLr), I’m not sure anything other than synthetic lethal attacks on the clonal driver will help. MLL rearrangements in young children have a particularly vile habit of swapping cell surface markers wholesale. They’re almost certainly more potent when they transform fetal liver progenitors, which seem to retain maximum plasticity. AA died prior to the introduction of second and third generation CAR-T, but stan riddell was part of her attending team, so I have to assume all the stops were pulled out. MG was different, 26yo Philadelphia-like ALL with 300k WBC refractory to everything. She should have been on ruxolitinib then transplanted. Her disease simply outran her T cells’ ability to divide. It was unreal. And she was a single mom. I will never forget either case. Even as just an “attached” fellow, it’s hard to watch. More so (for me at least) than older patients where you can reasonably guess what’s coming next. It just feels so unjust. Anyways. Let’s hope I’m wrong and 2nd/3rd gen auto and allow CAR-T can put these kinds of cases into durable remission for the rest of their, hopefully long and healthy, lives. Because right now, nothing does.

GeekyBear 7y ago

Vice on HBO did an episode back in 2015 looking at several different experimental (at the time) cancer treatments which included a segment on the fourth patient to receive CAR-T. https://www.youtube.com/watch?v=FlK-PeCfezM https://www.youtube.com/watch?v=FlK-PeCfezM The CAR-T segment starts at 27:30.

Circuits 7y ago

If cancer was a dude I would punch him in face.

aiyodev 7y ago

> They are frozen in liquid nitrogen and sent to laboratories in the United States. Why do you need to send your blood to an “inferior” healthcare system?