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by ekianjo 3544 days ago
> That seems like a small improvement rather than a "game changer."

It shows you are not really aware of the state of Cancer drugs these days. Drugs that can make 20~30% patients live 3 months longer are usually considered pretty good, doubling the percentage of survival in ADVANCED cancer is certainly unheard of.
1 comments
OrthoMetaPara 3544 days ago
That's a pretty pathetic standard for "good"

Chimeric Antigen Receptor therapy seems like more of a "game changer," given that it's a new therapeutic direction. This is just another monoclonal antibody.

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apathy 3543 days ago
Spoken like someone who hasn't been following the Kite trials...

Also of note: just like good ol' mAbs, you need a target for CAR-T cells. And BiTEs, and BiKEs, and what have you.

Also also of note: the approaches that took pediatric ALL and adult APL (among others) from 5-10% survival to 90-95% survival weren't single pronged. (Good thing, too; I've seen patients who seemed ideal for CAR-T die when their malignancy outran the engineered cells) The majority of progress in real-world outcomes has arisen from combination or sequential therapies, incrementally improved to decrease toxicity and maximize efficacy.

Which is to say, incrementally advanced.

Last: per the above, you can use the two together. If a tumor is actively suppressing T cells, it isn't going to dissolve from CAR-T cells without a fight. There are additional tactics useful for "priming" the immune system, but in the end I don't see a lot of solid tumors melting away in trials of CAR-T cells (feel free to correct me).

Do take a look at the Kite trials and how they're structured. When you have to condition a patient with fludarabine to hit outcomes (at all) that's not a wonder drug. It's another tool in the toolbox. A necessary and useful tool, but a tool, not a magic wand.

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apathy 3543 days ago
Hey, just so I'm not a total hypocrite, it turns out that you can "turn off" PD-1 and PD-L1 response in CAR-T cells (at least in mouse models, https://www.jci.org/articles/view/83092 ). In the end I stand by my contention that it's a tool and it needs to be used for the right jobs, but it's a very versatile tool.

I work on immunosenescence and immune stimulation (the real thing) in oncology, and I happen to believe that we do many patients a disservice by nuking their immune systems with chemo and then relying on things like TKIs or BiTEs to pick up the mess. But it's also important to keep in mind that Gleevec alone didn't get rid of CML, and the way ALL and APL were managed up to 95% cure rates is by adding a little poison (As2O3, methotrexate, etc.) to the brew (asterisk) to finish things off. It's a delicate balance. I think it always will be.

(asterisk: ok more like a metric fuckload of poisons for ALL. But the real trick is "resurrecting" the patient with leukovorin after folate starvation essentially kills them.)

http://blogs.sciencemag.org/pipeline/archives/2016/07/08/car...

Look up the SuperMAB saga for more cautionary tales. Plenty of people have died from chemo and immunosuppression too (nobody benefits from lungs full of aspergillus and a gut full of C. diff). If it were easy, somebody would have figured it out already :-)

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coldtea 3543 days ago
>That's a pretty pathetic standard for "good"

The standards are set by reality, not wishes.

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dfsegoat 3543 days ago
>> This is just another monoclonal antibody.

That is like saying "this is just another GPS guided smart weapon". Just because mAbs aren't new, doesn't mean they don't have enormous therapeutic potential.

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ekianjo 3543 days ago
> That's a pretty pathetic standard for "good"

Thats because there is almost no low hanging fruit for cancer treatment and therefore you only get incremental progress most of the time.

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