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'Living drug' offers hope to terminal blood cancer patients

bbc.co.uk

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Re: 'Living drug' offers hope to terminal blood cancer patients

#31

Post by DrJosiah »

lliamander wrote: post #28
DrJosiah wrote: post #27

Earlier quoted context omitted.

(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.

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).

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.

Re: 'Living drug' offers hope to terminal blood cancer patients

#33

Post by dannykwells »

lliamander wrote: post #25
dannykwells wrote: post #19

Earlier quoted context omitted.

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 a…

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?

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).

Re: 'Living drug' offers hope to terminal blood cancer patients

#34

Post by kennyloginNTH »

dhimes wrote: post #18
WalterBright wrote: post #9

Earlier quoted context omitted.

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?

Big oil killing zombie legalization

Re: 'Living drug' offers hope to terminal blood cancer patients

#35

Post by WalterBright »

SketchySeaBeast wrote: post #22
WalterBright wrote: post #11

Earlier quoted context omitted.

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 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?

The first scene was indeed there, but then played no role for multiple seasons.

Re: 'Living drug' offers hope to terminal blood cancer patients

#36

Post by WalterBright »

DennisP wrote: post #14
WalterBright wrote: post #11

Earlier quoted context omitted.

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.

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.

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.

Re: 'Living drug' offers hope to terminal blood cancer patients

#37

Post by WalterBright »

sapilla wrote: post #23
WalterBright wrote: post #9

Earlier quoted context omitted.

I wouldn't worry about zombies. They violate conservation of energy laws, for one.

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!)

Re: 'Living drug' offers hope to terminal blood cancer patients

#38

Post by lifeisstillgood »

NotSammyHagar wrote: post #4

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

Re: 'Living drug' offers hope to terminal blood cancer patients

#39

Post by apathy »

dannykwells wrote: post #19
apathy wrote: post #17

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 AM…

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 a…

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.

Re: 'Living drug' offers hope to terminal blood cancer patients

#40

Post by DennisP »

WalterBright wrote: post #36
DennisP wrote: post #14

Earlier quoted context omitted.

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.

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 Ar…

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?)

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