'Living drug' offers hope to terminal blood cancer patients(bbc.co.uk)
bbc.co.uk
'Living drug' offers hope to terminal blood cancer patients
https://www.bbc.co.uk/news/health-48706822
40 comments
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.
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.
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.
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.
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?
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?
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).
> For CAR-T therapy, the common remark is “you know it’s working when the patient goes to the ICU” from tumor lysis
Why is that not also true in chemo patients?
Why is that not also true in chemo patients?
(note, I'm not the right type of doctor to answer this properly, but my understanding is...)
A lot of chemos are some type of poison, only slightly worse for the tumor than it is for the rest of your body. It doesn't die fast enough (and if it did, you'd be killing the rest of you too). Think months / years with chemo vs. weeks with CAR-T.
A lot of chemos are some type of poison, only slightly worse for the tumor than it is for the rest of your body. It doesn't die fast enough (and if it did, you'd be killing the rest of you too). Think months / years with chemo vs. weeks with CAR-T.
Ah, so it just kills it faster?
I know a child with leukemia who recently started chemo. They had him on sodium bicarbonate and other medication to reduce the acidity of his urine (to compensate for the increased amount of uric acid). However, they only had him on it for the first few days of chemo. My understanding was that the bulk of the chemolysis occured in that period (though I could be mistaken).
I know a child with leukemia who recently started chemo. They had him on sodium bicarbonate and other medication to reduce the acidity of his urine (to compensate for the increased amount of uric acid). However, they only had him on it for the first few days of chemo. My understanding was that the bulk of the chemolysis occured in that period (though I could be mistaken).
It kills specifically. The immune therapies are turning your (or someone else's) body's T cells into murder machines, tuned specifically for a target. And because it is so good at its job, cleaning out the biological waste from destroying cancer is difficult, so trips to the ICU are not uncommon.
Chemo kills everything in your body, just the cancer a little bit more. You do the chemo, wait a few weeks, then do chemo again, wait a few weeks, maybe get a scan, do chemo again, wait a few weeks, ..., maybe in 6 months if your treatments are going well you keep going, maybe they switch you to something else, maybe this round is done and you take a break for a while. You wait because if you don't, the poison kills all of you, not just the cancer.
Chemo kills everything in your body, just the cancer a little bit more. You do the chemo, wait a few weeks, then do chemo again, wait a few weeks, maybe get a scan, do chemo again, wait a few weeks, ..., maybe in 6 months if your treatments are going well you keep going, maybe they switch you to something else, maybe this round is done and you take a break for a while. You wait because if you don't, the poison kills all of you, not just the cancer.
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.
Thank you
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
The CAR-T segment starts at 27:30.
https://www.youtube.com/watch?v=FlK-PeCfezM
The CAR-T segment starts at 27:30.
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.
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/
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.
Oh I see, sorry about the confusion.
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
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?
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?
> 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?
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.
Not starting in the UK. These therapies were invented and first approved in the US (CAR-T was invented at Penn and MSKCC)
I wouldn't worry about zombies. They violate conservation of energy laws, for one.
They violate conservation of energy laws
Now I'm even more worried! How can the do that?
Now I'm even more worried! How can the do that?
Also, how do they move if their muscles have rotted away and they have no functioning circulatory system?
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.
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.
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.
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.
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.
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.
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
(As for GoT, how many movies have had dragons?)
(As for GoT, how many movies have had dragons?)
I'm guessing they didn't stick around for the dragons.
> 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?
So the very first scene of both the books and tv show?
The first scene was indeed there, but then played no role for multiple seasons.
Where do zombies violate conservation of energy? They do wear down eventually, and fresh brains are low entropy and also nutrient dense.
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!)
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!)
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They also use a HIV like virus as the vector to modify the T-Cells in the first place!
Relevant xkcd: https://xkcd.com/938/
I thought it sounded a bit like one of the Witcher trials.
So gene therapy with extra steps.
If cancer was a dude I would punch him in face.
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)