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Training the Immune System to Fight Cancer
September 14, 2011 6:22 AM   Subscribe

At first, nothing happened. But after 10 days, hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. His blood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst. A few weeks later, the fevers were gone. And so was the leukemia. - (NYT Link)
posted by Slap*Happy (63 comments total) 42 users marked this as a favorite

 
Amazingly, the entire article reads without one single reference to "a miracle." That in itself is a miracle.
posted by modemac at 6:25 AM on September 14, 2011 [24 favorites]


To modify their patients’ T-cells, Dr. June and his colleagues tried a daring approach: they used a disabled form of H.I.V.-1. They are the first ever to use H.I.V.-1 as the vector in gene therapy for cancer patients (the virus has been used in other diseases).

The AIDS virus is a natural for this kind of treatment, Dr. June said, because it evolved to invade T-cells. The idea of putting any form of the AIDS virus into people sounds a bit frightening, he acknowledged, but the virus used by his team was “gutted” and was no longer harmful.
And to those in the past who wondered why were spending money on a "gay disease" and no amount of "gay people are humans too" would convince them, I would now like to say: I told you so.

There is no way to predict what the outcome of research is going to be (that's why they call it research) and it could be huge.
posted by DU at 6:29 AM on September 14, 2011 [89 favorites]


Double.
posted by Johnny Wallflower at 6:30 AM on September 14, 2011


Double smubble, this is awesome.

Note to world: this is how you do science writing!
posted by JHarris at 6:37 AM on September 14, 2011 [7 favorites]


And to those in the past who wondered why were spending money on a "gay disease" and no amount of "gay people are humans too" would convince them, I would now like to say: I told you so.

Never stop telling them this. I'll them this this too if you like.
posted by JHarris at 6:39 AM on September 14, 2011 [1 favorite]


There is no way to predict what the outcome of research is going to be

Yes there is. The answer is zombies. All research inevitably leads to zombies. It's the Zombie Law of Research: for time/energy spent on research N, zombies.. uh.. look, I don't know this science stuff, because I don't want zombies. I don't know what YOUR problem is.
posted by curious nu at 6:48 AM on September 14, 2011 [8 favorites]


But the NYT article isn't a double, and is well written. Don't delete.

Also
DU: And to those in the past who wondered why were spending money on a "gay disease" and no amount of "gay people are humans too" would convince them, I would now like to say: I told you so.

JHarris: Never stop telling them this. I'll them this this too if you like.
I am a much worse person than either of you. I would like to tell them that there is a cure for their loved-one's cancer, but it requires shooting them up with "gay genes".
posted by benito.strauss at 6:48 AM on September 14, 2011 [38 favorites]


As a physician, I feel this post should be tripled, quadrupled. It's advances like this one that make possibly routine genetic tailored therapy even 20yrs from now.

I'm not sure why Time magazine ran a cover story on why Dr. Oz thinks salmon is good to eat AFTER this story came out, but it goes to show you where popular science is.....

More notes:

1. HIV research did help.

2. This amazing advance was funded through NIH grants in the University setting. Not in the pharmaceutical research sphere. Plenty of their so called big advances start like this. True, the machinery and production of this stuff on a large scale process won't happen in the university, but the discovery is academic based.

As much as people want to cry about what curtailing drug industry profits will do to R&D, remember the industry still on a whole spends 40% on marketing.
posted by skepticallypleased at 6:54 AM on September 14, 2011 [61 favorites]


I managed to both tear up and feel like I had a decent grip of the experimental process used in this trial. Good science writing indeed!
posted by chatongriffes at 6:58 AM on September 14, 2011


I would like to tell them that there is a cure for their loved-one's cancer, but it requires shooting them up with "gay genes".

Yoohoo, Mr. Falwell! Oh, right, dead. Mr. and Mrs. Bachmann? "Divine retribution for homosexuality", yes?
posted by likeso at 7:15 AM on September 14, 2011


Maybe we will eventually be able to cure the cervical cancer you got because the fundies didn't want you to get the HPV vaccine.
posted by localroger at 7:17 AM on September 14, 2011 [2 favorites]


This was predicted 40 years ago by Norman Spinrad in his short story Carcinoma Angels.
posted by Kirth Gerson at 7:20 AM on September 14, 2011 [4 favorites]


Yeah, the NYT article is way more accessible than the NEJOM, written with words instead of numbers, so the FPP probably just requires a "previously." Great read, great dedication on Horwich's part, staring at millionth-of-an-inch samples for years on end, and the article saved what was a particularly morbid Tuesday NYT (at least the front section).

I'm just in seriously in awe of Horwich's desk. Makes me wonder if one of us MeFites has been printing out all of his/her favorite threads over the years...
posted by obscurator at 7:21 AM on September 14, 2011


INT. TOBY'S OFFICE - FLASHBACK

ANDY
You're going to give me your white blood cells... not all of them, but as many as I want.

TOBY
Why?

ANDY
Because you love me.

TOBY
No, wha... uh... What's the matter with your white blood cells?

ANDY
Nothing. It's my immune system. It's not... recognizing that a pregnancy isn't something
it's supposed to attack. So, they draw blood from you... like a rabid dog -- clean it,
thank goodness... and give me injections of your blood cells to build up tolerance. You
know how you're always saying you wish people were more like you? Well... The guy's had a lot of success.
posted by ceribus peribus at 7:23 AM on September 14, 2011 [1 favorite]


This is boy-in-a-bubble level of awe-inspiring science.
posted by Theta States at 7:23 AM on September 14, 2011


Maybe we will eventually be able to cure the cervical cancer you got because the fundies didn't want you to get the HPV vaccine.

Ah, but no, localroger. A person would not be righteous if they made use of any treatment based on this, surely? (weg)

Fantastic, fantastic, fantastic. Thanks, Slap*Happy.
posted by likeso at 7:26 AM on September 14, 2011


Maybe we will eventually be able to cure the cervical cancer you got because the fundies didn't want you to get the HPV vaccine.

Indeed. Weirdly, but disturbingly, I wonder if we'll face a potential transition period when people assume all disease is "curable" this way, and attendant skepticism of vaccination and other public health approaches -- given that we already face vaccine skepticism as things are. That could be bad.
Not a concern troll, just thinking through the ramifications.

I wonder what the cost ROI is on this vs. prevention strategies?
posted by dhartung at 7:31 AM on September 14, 2011


Do you mean HPV or cancer? 'Coz if there are effective prevention strategies fr cancer, I haven't been hearing about them...

HPV, on the other hand, infects a kind of ridiculous proportion of adults at some point in their lives (over 50%, according to CDC), and often hangs out without any visible symptoms for years making it really hard to prevent transmission to others. Because you can have it and not even know it for a really long time.
posted by kaibutsu at 7:43 AM on September 14, 2011


This sounds... surprisingly promising. Can't wait to see where it goes.

As a tangent to the "gay disease" rhetoric... I was listening to a podcast from a couple years ago... Two straight, VERY pro-gay hosts (a man and a woman) were talking about how having unprotected sex was dangerous, because you know - the herpes, the clap, etc. A guest brought up "What about, you know, the *HIV*??" and both of them said "Oh no, that's not a concern for straight people, really. It's mostly gays that get it." - I had to double check that the date on the podcast was 2008, not 1988. I can't believe there are still people out there who think that HIV is disease that only gay (or maybe, bisexual) people get. Of course, these are also the same people who heard the stat about 80% of American adults having oral herpes (ie cold sores), and confusing it with genital herpes and saying that they're never going to fuck another person again. So perhaps their sexual edumacation wasn't exactly the best to begin with.
posted by antifuse at 7:44 AM on September 14, 2011


Dr. Baltar, is that you?
posted by tzikeh at 7:48 AM on September 14, 2011 [1 favorite]


Super amazing, exciting, astonishing, glorious progress. My mother is a miraculous 30-year cancer survivor; her particular type had a 5% 5-year survival rate. Fuck Cancer, and much love for these researchers.

But:

It seems to me on first read that this is last-ditch, all-else-has-failed type stuff, given that the targeted protein on the cancerous cells also appears on healthy cells of the same type:
Mr. Ludwig’s disease, chronic lymphocytic leukemia, is a cancer of B-cells, the part of the immune system that normally produces antibodies to fight infection. All B-cells, whether healthy or leukemic, have on their surfaces a protein called CD19. To treat patients with the disease, the researchers hoped to reprogram their T-cells to find CD19 and attack B-cells carrying it.

...

The treatment wiped out all of the patients’ B-cells, both healthy ones and leukemic ones, and will continue to do for as long as the new T-cells persist in the body, which could be forever (and ideally should be, to keep the leukemia at bay). The lack of B-cells means that the patients may be left vulnerable to infection, and they will need periodic infusions of a substance called intravenous immune globulin to protect them.
...which means a compromised immune system that requires lifelong management, yes? Additionally, in other patients:
Engineered T-cells have attacked healthy tissue in patients at other centers. Such a reaction killed a 39-year-old woman with advanced colon cancer in a study at the National Cancer Institute, researchers there reported last year in the journal Molecular Therapy.

She developed severe breathing trouble 15 minutes after receiving the T-cells, had to be put on a ventilator and died a few days later. Apparently, a protein target on the cancer cells was also present in her lungs, and the T-cells homed in on it.
ZakDaddy's Hope: That through Science! researchers discover an even better way to selectively target cancerous cells and leave healthy tissue alone. Godspeed.
posted by ZakDaddy at 7:58 AM on September 14, 2011 [2 favorites]


ZakDaddy raises my question after reading the article--is this treatment going to work for everyone with leukemia or was this patient a special circumstance?
posted by LarryC at 8:02 AM on September 14, 2011


This! This is what we are always striving for, hoping for. For everyone who thinks that a bunch of mad scientists are sitting up in a tower plotting to cause autism, this is what we are doing. We are working to make progress.

Sometimes major progress happens on a few patients in a Phase I safety trial and we use that information to make something more available to the masses. I don't know how useful this will be to the average leukemia patient, but it advances cancer (and HIV, and retrovirus) research forward and that is brilliant.
posted by Sophie1 at 8:05 AM on September 14, 2011 [9 favorites]


Yeah, but to my layman's eye, that's the issue with most cancer treatments: How to destroy the cancer without destroying everything else.
posted by Stagger Lee at 8:06 AM on September 14, 2011 [3 favorites]


Leukemia killed the best friend I ever had, and I'd like to see it vanquished within my lifetime. I'm not one for casual use of profanity, so believe me when I say Fuck Cancer.
posted by Soliloquy at 8:17 AM on September 14, 2011 [10 favorites]


is this treatment going to work for everyone with leukemia or was this patient a special circumstance?

This is precisely what these doctors, and likely many more after them, will now try to determine. That's what the scientific method looks like. Do different proteins need to be used to tailor this type of treatment to different types of cancer? Or is it that the patient was special, and why would that be?

It's a breakthrough, but as the doctors interviewed in the article – and the writer of the article, thankfully – go to great pains to point out, it's not a viable treatment for many people until many of the details are sorted out.
posted by dammitjim at 8:22 AM on September 14, 2011 [2 favorites]


This is really exciting stuff. Cancers always develop under a selective pressure to look very similar to healthy cells -- otherwise the normal, unmodified immune system would pick them off easily -- so picking targets by which your modified T cells can recognise them is tricky. CD19 isn't really an optimal choice because it's expressed on a load of healthy cells too, so your modified T cells are killing a load of normal healthy cells in addition to the cancer, and you get some nasty side effects. So, yeah, targeting of the treatment is always a really difficult part of fighting cancer.

However, the the seriously hard work was establishing the system and demonstrating some safety and efficacy in patients; because of the way they designed the system, it should be pretty easy to swap out the anti-CD19 molecule for one targeting pretty much anything else we decide we're interested in. Regulatory issues make this sort of study quite slow-moving, so it's likely that June's lab picked CD19 as a target a while ago and has had to just stick with it to avoid re-starting the entire build-up to the clinical trial. Since they started, a handful of seemingly more specific and therefore potentially better targets have been identified. Labs around the world -- including June's lab, and including a couple of people in my institute -- are already working on assessing these, and making their own variants on June's system to target them, ready for testing. So the exciting thing about this study isn't this particular treatment -- although it is cool -- it's the demonstration of a platform upon which a load of new, powerful treatments can potentially be built.

This is many years away from widespread application, for a bunch of reasons including the enormous amount of work and expensive reagents currently required to generate the modified T cell population for each patient, and the inevitable safety concerns that come up when playing with the immune system (it's complicated, and its behaviour can be hard to predict) and with viruses that slot themselves into the genome (if you're unlucky, they can turn the modified cells cancerous). But this is stuff we're rapidly getting much better at. IMO, this is one of the big therapeutic strategies to bet on over the next decade or two, and it's great to see it demonstrated in the clinic.

[Disclosure: I work in a closely related field and have colleagues who work on something extremely similar. Neither I nor my colleagues stand to gain financially from this stuff, I just really am this excitable.]

This is boy-in-a-bubble level of awe-inspiring science.
Yeah. Let's hope it ends a little better than that one.

ZakDaddy raises my question after reading the article--is this treatment going to work for everyone with leukemia or was this patient a special circumstance?
IIRC, all leukemia patients should have CD19 on their cancerous cells, and should therefore be able to benefit from this treatment or one based on it. Eventually, it shouldn't be too hard to broaden this treatment technique to attack all sorts of diseases. This is all a long way off though, for the reasons I mention above.

Yes there is. The answer is zombies. All research inevitably leads to zombies. It's the Zombie Law of Research: for time/energy spent on research N, zombies.. uh.. look, I don't know this science stuff, because I don't want zombies. I don't know what YOUR problem is.

In fairness, it's not all science... I think it's just all genetic engineering. 28 Days Later, Silent Hill, I Am Legend (the re-make, anyway), Dawn Of The Dead (most recent re-make)... all caused by genetically modified viruses gone out of control. Rise of The Planet of The Apes and Deep Blue Sea are about genetically modified animals, and I think the BBC's recent re-make of Day Of The Triffids had the triffids as a GM crop. On the upside, the most recent Spiderman (Toby Maguire) got his powers from a genetically modified spider, so it's not all bad. "Genetic Manipulation" is the 21st century's version of the "mysterious radiation" plot device.

Tangentally, when I Am Legend came out I was working on almost exactly the same research project as Will Smith's character, a fact which a remarkable number of women in bars found entirely unimpressive. Maybe if I had his research project and his rippling abs?
posted by metaBugs at 8:22 AM on September 14, 2011 [27 favorites]


Don't worry, your HMO won't cover it anyway.
posted by blue_beetle at 8:28 AM on September 14, 2011 [7 favorites]


Tangentally, when I Am Legend came out I was working on almost exactly the same research project as Will Smith's character, a fact which a remarkable number of women in bars found entirely unimpressive.

Science! So there's something it cannot do. For the rest though, Hurrah!
posted by chavenet at 8:29 AM on September 14, 2011


A guest brought up "What about, you know, the *HIV*??" and both of them said "Oh no, that's not a concern for straight people, really. It's mostly gays that get it." - I had to double check that the date on the podcast was 2008, not 1988. I can't believe there are still people out there who think that HIV is disease that only gay (or maybe, bisexual) people get.

I have no knowledge of this podcast or anything but if they were speaking on a purely statistical basis they're not that wrong. Now, that's a moronic thing to base your actions on - you may be way more likely to get the clap from your reckless heterosexual behavior but why would you risk either? Just because it's not likely you'll get hit by lightning is no reason to run around the golf course in the thunderstorm.

But look at the numbers and yeah, you should be way more worried about HIV if you're a gay man.
Overall, CDC’s new incidence estimates continue to show that

Gay and bisexual men remain the population most heavily affected by HIV in the United States. CDC estimates MSM represent approximately 2% of the US population, but accounted for more than 50% of all new HIV infections annually from 2006 to 2009 –56% in 2006 (27,000), 58% in 2007 (32,300), 56% in 2008 (26,900) and 61% (29,300) in 2009.
So out of 100% if you drop the 12% related to injection drugs you have 61% from male to male sex and 27% from male/female sex, (my understanding if that female-female HIV transmission is so small as to be statistically irrelevant) a more than 2:1 ratio. That 27% of the roughly 50,000 new HIV cases a year, or 13,500.

Use the CIA factbook stats on how many people there are from 15 to 65 and you get 104,411,352 men and 104,808,064 women - just shy of 210 million. Divide it by 13,500 and you have one case for every 15,497 people.

Compare that to the CDC stats for Gonorrhea, which put the annual incidence rate at about 1 in 1,000.

Compare that to being a man having sex with men. If we stay with the same organization's numbers they're turning up a 2% of the population having male-male sex. Stick with the CIA's 15 to 64 population numbers (since we used them for the last calc) and that's 2.1 million dudes sharing 30,500 new cases in a year - 1 in 101.

So when one group has a 1 in 100 chance and another has a 1 in 15,497 chance? Yeah, that is tremendously more of a concern for one group than the other.

You'd have to be a complete moron to use this as a reason to behave recklessly (or as a reason not to treat it as the public health issue that it is & try to stop it) but HIV continues to be a problem for the gay community in a way it isn't for heterosexuals.
posted by phearlez at 8:37 AM on September 14, 2011 [13 favorites]


Wow.

You know, yes, fuck cancer. But also, fuck the anti-science crazies dominating our national discourse too. We need to shake people by the shirt and say, "look, you assume a standard of living, a level of healthcare, a robust scientific enterprise that gives you these things, as a basis for living in the 21st century at all. You are typing on a computer, taking blood pressure medication, and otherwise not lonely or dead because of science. You cannot selectively choose which science you're going to respect and which you're going to counter with improbably fairy tale explanations that inhibit progress; nor can you selectively defund science and education and continue to expect science to be there the next time a pathogen jumps the antibiotic resistance fucking turnstile or your baby needs a c-section to come into this world or you rely on technology in any other way."

Mr. Huntsman, you're welcome.
posted by spitbull at 8:44 AM on September 14, 2011 [14 favorites]


XKCD

"Ok, so I have blood cells growing out of control, so you're going to give me different blood cells that ALSO grow out of control?"
"Yes, but it's ok, because we've treated THIS blood with HIV!"
"Are you sure you're a doctor?"
"Almost definitely."

Apparently pancreatic cancer is on their target list. Pancreatic cancer took down my Mom. Some part of me wants to deliberately misunderstand the results so that I can believe they're giving cancer AIDS. Can we give cancer smallpox next, or black lung, maybe polio? Fuck cancer, that's how. I want it to suffer before it dies.
posted by justsomebodythatyouusedtoknow at 8:51 AM on September 14, 2011 [4 favorites]


I love this. I love that we can engineer the immune system to recognize targets that it cannot recognize on its own.

But while I love the potential, I'm also wary of the obstacles which must be overcome. It sounds like T-cell replication is still a big deal, as is the potential for toxicity from the tumor cells themselves lysing. That's what trials are for though; we have the right idea, we have some encouraging results, now it's time to work on the specifics so that we can identify the proper targets, engineer an environment to efficiently replicate T-cells, and eventually turn this into a mainstream therapy to reduce suffering.

Seriously, I love me some science.
posted by Turkey Glue at 8:54 AM on September 14, 2011


Leukemia killed my dad one year ago this week. Near the end, he said, "I wonder how long after I am gone before people will not have to endure this?" I had no answer. I wish I could show him ths article.
posted by Senator at 8:56 AM on September 14, 2011 [13 favorites]


The treatment increases your T-cell count while reducing your B-cell count, meaning that you end up less resilient to new diseases. I think the levels might return to normal after a while? Anyway, surely a risk worth taking if you're a leukemia patient, but since the treatment does use a modified HIV, you should really be celibate for a while afterward.
posted by LogicalDash at 9:02 AM on September 14, 2011


This progress is full of win. Thanks for posting.
posted by arcticseal at 9:03 AM on September 14, 2011


On re-reading: I really need to stop making wall-o'-text comments on sciency posts. I'll tone it down a bit in future.
posted by metaBugs at 9:05 AM on September 14, 2011


Logical dash - I don't see why someone would need to be celibate. It's inactivated HIV. Subjects will likely test antibody positive, but that was almost definitely in the consent form, they know that, and the study will likely do long-term RNA testing for actual virus.

At least that's what I'd ask for if I was on the IRB reviewing this study.
posted by Sophie1 at 9:07 AM on September 14, 2011


In fairness, it's not all science... I think it's just all genetic engineering. 28 Days Later, Silent Hill, I Am Legend (the re-make, anyway), Dawn Of The Dead (most recent re-make)... all caused by genetically modified viruses gone out of control.

look, if this is your idea of "scientific accuracy", mister
posted by This, of course, alludes to you at 9:18 AM on September 14, 2011 [2 favorites]


look, if this is your idea of "scientific accuracy", mister
Oops, you're right. I was thinking of Resident Evil.
posted by metaBugs at 9:22 AM on September 14, 2011 [3 favorites]


Turkey Glue writes "as is the potential for toxicity from the tumor cells themselves lysing."

If this turns out to be a known side effect of the treatment would it be possible to deal with the toxins with dialysis? IE: here have this shot of modified T-Cells and let me hook you up to this machine for a week while the T-cells do their work.
posted by Mitheral at 9:38 AM on September 14, 2011 [1 favorite]


Daydreaming out loud here ... I wonder ... if this type of therapy proves successful, will it tilt US policy in favor of national health care? After the first few proof-of-concept tests (which cherry-pick the easiest* targets, like CD19) this kind of approach will probably require a lot of personalization because there aren't too many one-size-fits-all targets that suit the normal industrial production methods for drugs. Personalized medicine requires developing a unique (or nearly unique) product for each patient, which is mindblowingly expensive.

At the same time, the unwritten rule in biomedical science (including the biotech industry) is that it's easiest to get funding for research on diseases that Congressmen are worried about getting. So if you're working on treatment for something that afflicts middle-aged straight white-collar males, and is too expensive for even Congressmen and their social circle to afford, maybe they'll decide Uncle Sam should foot the bill after all.

*For ridiculously hard values of "easy"
posted by Quietgal at 10:03 AM on September 14, 2011 [1 favorite]


So let's say that at some point we perfect a way to "paint" undesirable cells with protein markers that can then be targeted by an engineered HIV strain...

Could you also paint fat cells? I'm picturing a future where the elite wealthy go to a mountain clinic, undergo a month of hellish fever, and come out as thin as they'd like to be, with all of their problem areas trimmed professionally by a designer virus.
posted by codacorolla at 10:04 AM on September 14, 2011


Science! So there's something it cannot do. For the rest though, Hurrah!

My brain read this in Zoidberg's voice.
posted by hippybear at 10:06 AM on September 14, 2011 [11 favorites]


So let's say that at some point we perfect a way to "paint" undesirable cells with protein markers that can then be targeted by an engineered HIV strain...

...I'm picturing a future where the elite wealthy go to a mountain clinic...


That's what you're picturing? I'm wondering about the future of bioweaponry. Bioterrorism research could provide at least two more avenues for securing additional funding.
posted by ceribus peribus at 10:23 AM on September 14, 2011


Yeah, but to my layman's eye, that's the issue with most cancer treatments: How to destroy the cancer without destroying everything else.

That is precisely the problem with almost every cancer we know of. The cancer is made of your own cells, but they're cells that decided to rebel against your tyrannical control of their growth and differentiation. 'Down with the despot, down with the autocrat!' they cheer as they multiply, seeking the freedom to grow and develop as 'independent' (yet schmucking off of your nutients) life wherever they damn well please.

Unlike the freedom fighters in reality, however, these guys do not wear nifty armbands and hats to differentiate them from some regular Joe off the street. Their hair looks different, but you can't get a bullet to take into account hair color when it kills someone. A trained assassin though, he'll look for that hair and yank it backwards as it slits that bastard recidivist cancer's throat...

Whoa there. Whoa, that... that went a little far. Anyway, yes, you are correct. And this is both awesome and the beginning of I am Legend (movie version).
posted by Slackermagee at 10:48 AM on September 14, 2011 [3 favorites]


It seems to be a recurring theme of the Universe that even the most vile and loathsome things can be repurposed for good - if we only have the will.
posted by Poet_Lariat at 10:50 AM on September 14, 2011 [1 favorite]


Also, if you want Congress to get this into some kind of national program, you have to sell it with sex. Its a potential cure for testicular, prostate, and breast cancer. Thats the trifecta of pain the dirty old men in the senate will approve of beating.
posted by Slackermagee at 10:55 AM on September 14, 2011


Smart people are, once more, smart.
posted by TheRedArmy at 11:05 AM on September 14, 2011


On re-reading: I really need to stop making wall-o'-text comments on sciency posts. I'll tone it down a bit in future.
posted by metaBugs


We disagree, we like when you do this.
posted by haveanicesummer at 11:12 AM on September 14, 2011 [7 favorites]


Daydreaming out loud here ... I wonder ... if this type of therapy proves successful, will it tilt US policy in favor of national health care?

People were cheering the other night over the thought of someone being left to die because they couldn't pay for medical care.

So, no.
posted by dirigibleman at 11:15 AM on September 14, 2011 [1 favorite]


This is all great, but have we got to the point where we can grow dinosaurs from DNA extracted from a mosquito trapped in amber yet?

Cause I'm really looking forward to that.
posted by mmrtnt at 11:56 AM on September 14, 2011 [2 favorites]


Just jumping in to say that the NYT article is indeed ridiculously well-written. It actually includes a fair bit of scientific content about what the researchers did, cautions about the drawbacks of an n=3 trial, and is perfectly understandable to the lay person. If only all science journalism worked like this.

Also, the trial is particularly impressive, because the people affected were more or less knocking on death's door, and out of treatment options before joining the trial.
posted by schmod at 11:57 AM on September 14, 2011 [1 favorite]


have we got to the point where we can grow dinosaurs from DNA extracted from a mosquito trapped in amber yet?

Actually (and I can't find the actual mention of it right now), but I heard someone somewhere state that they've actually been looking at doing that, but that DNA generally doesn't last intact enough across millennia to do that kind of thing, so barring a giant leap forward in our detection and assembly technology this will likely never be possible.

Oh, wait, I remember now. Hang on.

Here we go: Jack Horner on Building A Dinosaur From A Chicken
posted by hippybear at 12:41 PM on September 14, 2011


but that DNA generally doesn't last intact enough across millennia to do that kind of thing, so barring a giant leap forward in our detection and assembly technology this will likely never be possible.

'salright, random monsters from corrupted dinosaur DNA will do just fine.
posted by Zed at 4:10 PM on September 14, 2011 [1 favorite]


Do you mean HPV or cancer? 'Coz if there are effective prevention strategies fr cancer, I haven't been hearing about them...

The best prevention strategy for cancer is to not smoke. Avoiding infections (such as HPV) that cause cancer is also a good prevention strategy. HPV causes several kinds of cervical cancer.
posted by grouse at 4:12 PM on September 14, 2011


I remember distinctly my Immunology prof in grad school some twenty five years years ago predicting, with certainty, that we'd have therapies just like this today. Against cancer. In the next breath, he predicted that no such thing would happen with AIDS. I had hoped he was half wrong.
posted by readyfreddy at 6:43 PM on September 14, 2011


So, my neighbor had some sort of cancer treatment for a nicely localized tumor that involved injecting the center of the tumor with some sort of modified tuberculosis cells or something along those lines - so apparently this idea of attacking cancer with other deadly diseases isn't entirely new?
posted by eviemath at 6:27 PM on September 15, 2011


This idea isn't new at all—people have had similar ideas for decades and it relies on groundwork developed by other scientists—but having it actually work is very new and exciting.

If you are talking about Bacillus Calmette-Guérin therapy, it's not really the same thing as using a modified HIV vector to perform gene therapy. In the BCG case, you're just using the attenuated bacillus to induce an inflammatory response. In neither case is the other deadly disease used to directly attack the cancer, but it used to provoke the immune system into doing it.
posted by grouse at 7:34 PM on September 15, 2011


So, my neighbor had some sort of cancer treatment for a nicely localized tumor that involved injecting the center of the tumor with some sort of modified tuberculosis cells or something along those lines - so apparently this idea of attacking cancer with other deadly diseases isn't entirely new?

I think we're talking about subtly different things. The two broad approaches to using pathogens against cancer are (a) introducing a pathogen (or parts of a pathogen) to provoke an immune response near the tumour; and (b) introducing a pathogen that will directly attack the tumour.

The BCG therapy sounds like an example of the former. I have the impression that the point isn't to have the pathogen attack the cancer cells. Instead, the presence of the pathogen causes the immune system to start ramping up a response in that area. As part of this response, immune cells in that site start becoming decidedly paranoid and -- if all goes to plan -- suddenly notice that the tumour cells aren't *quite* what they're supposed to be, and mount an attack against the tumour as well as against the pathogen. If that sounds a bit hand-wavey it's because it is; I'm not an immunologist and I haven't really paid much attention to this branch of treatment efforts recently. Hopefully someone better informed can correct me.

The latter generally revolves around modifying a virus in such a way that it's only able to attack cancer cells. Most cancer cells have very similar broad functional properties: DNA and protein synthesis machinery constantly switched on, no need for external growth signals and an ability to ignore various signals telling it to commit suicide.* These are more or less the same characteristics that a virus would normally need to manipulate its host cell into having. So you remove the genes responsible for this stuff from the virus and stick your crippled virus into the patient: viruses that get into healthy cells can't do anything, viruses that get into cancer cells are able to replicate and kill the cell as normal. Or you can take a different approach and modify your virus such that the "transcription factor" (a protein responsible for switching expression of a particular gene on) that your virus needs to start its replication isn't one of the really common ones, but something weird that's only found in particular kinds of cancer.

You can mix and match these approaches along with some other tweaks, for example a pathogen that does attack tumour cells while simultaneously trying to attract the attention of the immune system.

With all that said, the approach talked about in the article is actually very different from both the BCG approach and the "giving the cancer a virus" approach. Here, they're not actually putting the HIV anywhere near the cancer cells, or even into the patient. They're using a heavily modified form of HIV to insert a stretch of DNA into the patient's own (healthy) T lymphocytes, a subset of their white blood cells / immune cells, that are growing in a dish in the lab. Once the DNA is in those cells, the HIV's job is done. That DNA encodes instructions to make a molecule that sticks out of the T cell's surface, that will bind to another molecule (called CD19) known to be on the surface of the cancer cells. These modified T cells are grown up in huge numbers (simply managing to grow the things without irrevocably changing them into a less useful form is something of a breakthrough in itself) and stuck back into the patient. When the new receptor on the modified T cell binds to the CD19 on the cancer cell, it triggers the T-cell's usual "attack" sequence, causing the T cell to kill the cancer cell.

So instead of attracting the patient's immune system to the general area of the tumour and hoping for the best, with this approach the scientists have specified a target entirely of their own choosing, and directly re-programmed the T cells to go hunting for it. It's a huge leap forward in our ability to control the immune system to our own ends, which has the potential to be applicable to all sorts of diseases.

*Although the details of how these functional changes are made are quite complex and widely variable between cancers, and sometimes even between different cells in the same tumour. So while most cancers look pretty similar if you stand back and squint a bit, taking a neat drug-based approach to treating cancer is hard because for virtually every patient you'll need a different suite of drugs to target their specific set of disrupted signalling networks. We're getting better at this -- sequencing (parts of) the DNA of patients' tumours is becoming the norm for certain kinds of cancer, to improve the accuracy of prognosis and to help pick the best treatment options -- but both our library of available drugs and our understanding of what a lot of the mutations we find actually mean are still very limited. One of the big bonuses of an approach like the one in the article -- which relies on spotting a marker on the cell's surface and then attacking from the outside -- is that we don't have to care about the intricacies of what's going on inside the cancer cells. It's like the difference between carefully hacking into the databases of a rival conclave of the Cabal organisation, and just paying off their security guards to stick a boot through the relevant server racks.
posted by metaBugs at 9:26 AM on September 16, 2011


There is one serious caveat from the article :

Engineered T-cells have attacked healthy tissue in patients at other centers. Such a reaction killed a 39-year-old woman with advanced colon cancer in a study at the National Cancer Institute, researchers there reported last year in the journal Molecular Therapy.

She developed severe breathing trouble 15 minutes after receiving the T-cells, had to be put on a ventilator and died a few days later. Apparently, a protein target on the cancer cells was also present in her lungs, and the T-cells homed in on it.


We always consider infectious diseases like Ebola as being deadly killers, but even the deadliest diseases don't kill within 3 days, much less make unaided breathing impossible within 15 min. All those diseases are fundamentally trying to survive themselves. T-cells otoh exist for one reason alone : to kill foreign cells.

Just musing. It's incredibly awesome to cure cancer, or any disease by programming your body's own immune system. Even this trial success required incredible awareness of virtually the proteins actually used by the body.
posted by jeffburdges at 8:46 AM on September 17, 2011


Maybe we will eventually be able to cure the cervical cancer you got because the fundies didn't want you to get the HPV vaccine.

Michele Bachmann chooses STD's
posted by homunculus at 9:17 AM on September 17, 2011


Excellent point, jeffburdges. There's a reason that for now, at least, this sort of therapy is only used in people who are considered terminal patients.
posted by grouse at 9:29 AM on September 17, 2011


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