The good kind of serial killer
August 10, 2011 12:25 PM Subscribe
"In each of the patients as much as five pounds of cancerous tissue completely melted away in a few weeks, and a year later it is still gone."
Chronic lymphocytic leukemia is the most common type of leukemia, usually striking older adults. The current accepted treatment is a bone marrow transplant, a complicated procedure that carries considerable risks and also requires a compatible donor. The University of Pennsylvania's Cancer Center has developed a new treatment that uses an HIV-derived vector to modify the patient's own T-cells to attack the cancerous tissue. A very limited test shows promising results.
The New England Journal of Medicine published the more detailed article today.
Chronic lymphocytic leukemia is the most common type of leukemia, usually striking older adults. The current accepted treatment is a bone marrow transplant, a complicated procedure that carries considerable risks and also requires a compatible donor. The University of Pennsylvania's Cancer Center has developed a new treatment that uses an HIV-derived vector to modify the patient's own T-cells to attack the cancerous tissue. A very limited test shows promising results.
The New England Journal of Medicine published the more detailed article today.
Interesting how the fluffy mainstream news link is on top, while buried at the bottom of the post is the NEJM report, which is a case report of one patient.
posted by serif at 12:32 PM on August 10, 2011 [14 favorites]
posted by serif at 12:32 PM on August 10, 2011 [14 favorites]
Please do not phrase preliminary science results in a way that may give false hope to those suffering from these diseases.
posted by benzenedream at 12:34 PM on August 10, 2011 [15 favorites]
posted by benzenedream at 12:34 PM on August 10, 2011 [15 favorites]
In similar past experimental treatments for several types of cancer the re-injected white cells killed a few cancer cells and then died out. But the Penn researchers inserted a gene that made the white blood cells multiply by a thousand fold inside the body.
That's the beauty of it! When winter rolls around, the gorillas freeze to death.
posted by atrazine at 12:42 PM on August 10, 2011 [6 favorites]
That's the beauty of it! When winter rolls around, the gorillas freeze to death.
posted by atrazine at 12:42 PM on August 10, 2011 [6 favorites]
SCIENCE BY PRESS RELEASE
posted by Slackermagee at 12:43 PM on August 10, 2011 [3 favorites]
posted by Slackermagee at 12:43 PM on August 10, 2011 [3 favorites]
Please do not phrase preliminary science results in a way that may give false hope to those suffering from these diseases.
Well, I generally agree pretty strongly with that, but...
Both the National Cancer Institute and several pharmaceutical companies declined to pay for the research. Neither applicants nor funders discuss the reasons an application is turned down. But good guesses are the general shortage of funds and the concept tried in this experiment was too novel and, thus, too risky for consideration.
A better guess might be that people whose kids go to college on the money made off of cancer treatment might be interested in keeping this kind of research pretty quiet, so any press they can get is good press, in this case.
posted by Rock Steady at 12:50 PM on August 10, 2011 [6 favorites]
Well, I generally agree pretty strongly with that, but...
Both the National Cancer Institute and several pharmaceutical companies declined to pay for the research. Neither applicants nor funders discuss the reasons an application is turned down. But good guesses are the general shortage of funds and the concept tried in this experiment was too novel and, thus, too risky for consideration.
A better guess might be that people whose kids go to college on the money made off of cancer treatment might be interested in keeping this kind of research pretty quiet, so any press they can get is good press, in this case.
posted by Rock Steady at 12:50 PM on August 10, 2011 [6 favorites]
The MSNBC article, fluffy as it is, covers an angle that I didn't find elsewhere - namely, the difficulty of getting funding for a really new treatment, particularly in this economy when funding is tight. It's sort of grim to think that "science by press release" may actually be a critical part of getting new treatments developed.
posted by restless_nomad at 12:50 PM on August 10, 2011 [6 favorites]
posted by restless_nomad at 12:50 PM on August 10, 2011 [6 favorites]
Whoa, blacked out there for a second after reading the MSNBC post and didn't go on to the NEJM article.
Not quite SBPR but damn close. I mean, really now, one person? I guess they did a whole bunch of preliminary safety stuff though which really helps to bulk out the publication but still. One person.
Statistically significant it ain't.
posted by Slackermagee at 12:52 PM on August 10, 2011
Not quite SBPR but damn close. I mean, really now, one person? I guess they did a whole bunch of preliminary safety stuff though which really helps to bulk out the publication but still. One person.
Statistically significant it ain't.
posted by Slackermagee at 12:52 PM on August 10, 2011
I mean, really now, one person?
The Penn press release link describes a "pilot trial of three patients." So that's a little better. I don't know why they only submitted the single case study to the NEJM, since apparently the results were uniformly positive.
posted by jedicus at 1:02 PM on August 10, 2011
The Penn press release link describes a "pilot trial of three patients." So that's a little better. I don't know why they only submitted the single case study to the NEJM, since apparently the results were uniformly positive.
posted by jedicus at 1:02 PM on August 10, 2011
The other two patients have chosen to remain anonymous but one who happens to be a scientist himself wrote, "I am still trying to grasp the enormity of what I am a part of(...)"
Uh-oh.
posted by Dmenet at 1:03 PM on August 10, 2011 [2 favorites]
Uh-oh.
posted by Dmenet at 1:03 PM on August 10, 2011 [2 favorites]
"Both the National Cancer Institute and several pharmaceutical companies declined to pay for the research. Neither applicants nor funders discuss the reasons an application is turned down. But good guesses are the general shortage of funds and the concept tried in this experiment was too novel and, thus, too risky for consideration."
Funding cuts hurt cancer research
posted by homunculus at 1:04 PM on August 10, 2011 [1 favorite]
Funding cuts hurt cancer research
posted by homunculus at 1:04 PM on August 10, 2011 [1 favorite]
Wow, what a breakthrough.
That treatment is no walk in the park though, unless your city happened to hire Hieronymous Bosch as its landscape architect.
posted by jamjam at 1:04 PM on August 10, 2011 [6 favorites]
That treatment is no walk in the park though, unless your city happened to hire Hieronymous Bosch as its landscape architect.
posted by jamjam at 1:04 PM on August 10, 2011 [6 favorites]
A third thought: this is just how the planet killer starts in the latest sci-fi medipocalypse movies. Viral cancer cure goes bananas, makes zombies/dead people/rage people/vampires.
posted by Slackermagee at 1:08 PM on August 10, 2011
posted by Slackermagee at 1:08 PM on August 10, 2011
"In each of the patients as much as five pounds of cancerous tissue completely melted away in a few weeks, and a year later it is still gone."
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posted by formless at 1:13 PM on August 10, 2011 [1 favorite]
LOSE WEIGHT NOW!
Find out how by purchasing Formless' revolutionary new weight-loss product: Leuk-aids. Lose weight the easy and fast way!
*note: AIDS and Leukemia are horrible diseases, and this advertisement is not meant to make light of the suffering many feel with them. Also, actual results may differ from 3 case studies. Call now!
posted by formless at 1:13 PM on August 10, 2011 [1 favorite]
To get better funding, label grant proposals:
Research for National Defense
posted by Postroad at 1:30 PM on August 10, 2011 [2 favorites]
Research for National Defense
posted by Postroad at 1:30 PM on August 10, 2011 [2 favorites]
"We're seeking a cure for the crippling affliction of not enough Predator Drones killing people with Hellfire missles. Thousands of men, women and children don't die each year from Predator strikes... but hopefully, with a bit more effort and funding, we can change that."
posted by FatherDagon at 1:37 PM on August 10, 2011 [2 favorites]
posted by FatherDagon at 1:37 PM on August 10, 2011 [2 favorites]
Statistically significant it ain't.
A low N can provide significance if the effect size is large enough. That is precisely what is being claimed here, so objecting to it on the basis of a low N is kind of silly. Simply having a low N tells you nothing about the significance of the result.
posted by Philosopher Dirtbike at 1:43 PM on August 10, 2011 [14 favorites]
A low N can provide significance if the effect size is large enough. That is precisely what is being claimed here, so objecting to it on the basis of a low N is kind of silly. Simply having a low N tells you nothing about the significance of the result.
posted by Philosopher Dirtbike at 1:43 PM on August 10, 2011 [14 favorites]
A better guess might be that people whose kids go to college on the money made off of cancer treatment might be interested in keeping this kind of research pretty quiet, so any press they can get is good press, in this case.
Or, it might be that this kind of therapy is inherently dangerous and has killed people in clinical trials before, so pharma is gunshy about funding it.
One downside from the paper: "Although CD19 is an attractive tumor target, with expression limited to normal and malignant B cells, there is concern that persistence of the chimeric antigen receptor T cells will mediate long-term B-cell deficiency. In fact, in our patient, B cells were absent from the blood and bone marrow for at least 6 months after infusion."
There are some fairly steep risks associated with this type of therapy, which is probably why pharma didn't touch it:
(a) the gene therapy going awry and cause cancer by itself
(b) the immune response being too strong and killing the patient, and the therapy is not readily titratable since it's self-replicating
(c) the epitope having some cryptic cross-reactivity that causes the immune system to go after the wrong target
That said, this is interesting work and I hope it goes on to phase II, where we might see what the actual cure rates are, and see if there are any really significant side-effects. The possibly permanent B cell depletion is moderately bad, but better than leukemia.
posted by benzenedream at 1:55 PM on August 10, 2011 [4 favorites]
Or, it might be that this kind of therapy is inherently dangerous and has killed people in clinical trials before, so pharma is gunshy about funding it.
One downside from the paper: "Although CD19 is an attractive tumor target, with expression limited to normal and malignant B cells, there is concern that persistence of the chimeric antigen receptor T cells will mediate long-term B-cell deficiency. In fact, in our patient, B cells were absent from the blood and bone marrow for at least 6 months after infusion."
There are some fairly steep risks associated with this type of therapy, which is probably why pharma didn't touch it:
(a) the gene therapy going awry and cause cancer by itself
(b) the immune response being too strong and killing the patient, and the therapy is not readily titratable since it's self-replicating
(c) the epitope having some cryptic cross-reactivity that causes the immune system to go after the wrong target
That said, this is interesting work and I hope it goes on to phase II, where we might see what the actual cure rates are, and see if there are any really significant side-effects. The possibly permanent B cell depletion is moderately bad, but better than leukemia.
posted by benzenedream at 1:55 PM on August 10, 2011 [4 favorites]
A better guess might be that people whose kids go to college on the money made off of cancer treatment might be interested in keeping this kind of research pretty quiet, so any press they can get is good press, in this case.
Science funding does not work how you think it works.
Pharm companies would rarely fund this kind of early stage, completely novel research. They're interested in safe bets, not risky new science projects.
And the NCI declining to fund this project due to some shadowy back room influence? We all know those guys spend most of the day smoking cubans lit with fistfuls $100 bills, so maybe they just didn't get around to reviewing the grant application before taking a swim in their money pit.
posted by Panjandrum at 2:05 PM on August 10, 2011 [3 favorites]
Science funding does not work how you think it works.
Pharm companies would rarely fund this kind of early stage, completely novel research. They're interested in safe bets, not risky new science projects.
And the NCI declining to fund this project due to some shadowy back room influence? We all know those guys spend most of the day smoking cubans lit with fistfuls $100 bills, so maybe they just didn't get around to reviewing the grant application before taking a swim in their money pit.
posted by Panjandrum at 2:05 PM on August 10, 2011 [3 favorites]
As someone with a loved one who is undergoing chemo (albeit for Lymphoma, not Leukemia, but still), I sure hope some philanthropist gives them a shit-ton of money to get some real clinical trials going. Because if this thing is real, it will be really fucking awesome.
posted by fancyoats at 2:20 PM on August 10, 2011
posted by fancyoats at 2:20 PM on August 10, 2011
Presumably this sort of therapy was tested in, eg., mouse models before being tried on actual humans? Can I talk someone with more initiative than me into searching out the results of such non-human trials? Three people seems like an awfully shady small sample size.
posted by eviemath at 2:44 PM on August 10, 2011
posted by eviemath at 2:44 PM on August 10, 2011
good on ya, benzenedream. spot on. That b-cell count persistence might be counteracted with some sort of regulation of whatever replication gene they inserted in the T-Cell, but I get your point.
I'm guessing that collection, isolation, and transduction of autologous t-cells is the most difficult and expensive part of this. Hopefully this spurs research into tumor-specific antigens for targeting for other cancers, since it says that they are not well defined. Showing that this kind of treatment can work and trying to adapt it for different cancers, maybe this would industrialize the process of producing said T-cells. There's your profit and what might get pharma to touch it.
posted by wayofthedodo at 2:53 PM on August 10, 2011
I'm guessing that collection, isolation, and transduction of autologous t-cells is the most difficult and expensive part of this. Hopefully this spurs research into tumor-specific antigens for targeting for other cancers, since it says that they are not well defined. Showing that this kind of treatment can work and trying to adapt it for different cancers, maybe this would industrialize the process of producing said T-cells. There's your profit and what might get pharma to touch it.
posted by wayofthedodo at 2:53 PM on August 10, 2011
My dear father died from this very thing 10 months ago. Bittersweet news.
posted by Senator at 2:54 PM on August 10, 2011
posted by Senator at 2:54 PM on August 10, 2011
There is one reference in the article to mice (Cmd + F 'mouse'):
Johnson LA, Morgan RA, Dudley ME, et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009;114:535-546
posted by a womble is an active kind of sloth at 2:55 PM on August 10, 2011
Johnson LA, Morgan RA, Dudley ME, et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009;114:535-546
posted by a womble is an active kind of sloth at 2:55 PM on August 10, 2011
After my day today, I don't really give a rat's ass if this is false hope. At least it's hope, and it's a hell of a lot better than despair. Hey Bill Gates--don't you have a bunch of extra money to hand out to deserving causes? Get on it!
posted by Go Banana at 2:56 PM on August 10, 2011
posted by Go Banana at 2:56 PM on August 10, 2011
collection, isolation, and transduction of autologous t-cells is the most difficult and expensive part of this
I'm not sure that's an issue, depending on how many T-cells you wanted. I've isolated millions of my own T-cells with some very basic equipment. There are even better higher-tech ways of doing it, too.
Viral transduction of primary tissue in culture is pretty routine. Purifying the packaged virus for human consumption could be costly/time-consuming.
I think that the biggest problem is monitoring the patient and hope that the transduced autologous T-cells don't get out of hand.
posted by porpoise at 3:02 PM on August 10, 2011
I'm not sure that's an issue, depending on how many T-cells you wanted. I've isolated millions of my own T-cells with some very basic equipment. There are even better higher-tech ways of doing it, too.
Viral transduction of primary tissue in culture is pretty routine. Purifying the packaged virus for human consumption could be costly/time-consuming.
I think that the biggest problem is monitoring the patient and hope that the transduced autologous T-cells don't get out of hand.
posted by porpoise at 3:02 PM on August 10, 2011
There's a long history of case studies in medical publication, and while they don't carry the same weight as randomized, longitudinal samples of thousands of patients, they do one thing very well: Demonstrate proof of concept.
This study does just that.
One data point can indeed be significant.
posted by yellowcandy at 3:03 PM on August 10, 2011 [4 favorites]
This study does just that.
One data point can indeed be significant.
posted by yellowcandy at 3:03 PM on August 10, 2011 [4 favorites]
depending on how many T-cells you wanted
can we do 3×10^8 T cells pretty easy? that's the number they used.
hope that the transduced autologous T-cells don't get out of hand
T-cell vaccination?
posted by wayofthedodo at 3:10 PM on August 10, 2011
can we do 3×10^8 T cells pretty easy? that's the number they used.
hope that the transduced autologous T-cells don't get out of hand
T-cell vaccination?
posted by wayofthedodo at 3:10 PM on August 10, 2011
Or it can be totally insignificant and just a freak.
You're missing the point. The one data point showing that something happened can illustrate without a shadow of a doubt that it is possible.
That's all 'proof of concept' is.
posted by yellowcandy at 3:16 PM on August 10, 2011
You're missing the point. The one data point showing that something happened can illustrate without a shadow of a doubt that it is possible.
That's all 'proof of concept' is.
posted by yellowcandy at 3:16 PM on August 10, 2011
The problem with that, yellowcandy, is that all sorts of flukes and biases and poor experiment design or other factors could be causing a false positive in the single data point. It's only a potential proof of concept.
posted by eviemath at 3:25 PM on August 10, 2011
posted by eviemath at 3:25 PM on August 10, 2011
(But if it works consistently in, say, mice, and then there's also a small number of human cases where it works, then you have a better argument for proof of concept.)
posted by eviemath at 3:26 PM on August 10, 2011
posted by eviemath at 3:26 PM on August 10, 2011
It's ridiculous to say that this isn't somehow "proper science." Yes, you're going to want to reproduce the results with a much larger cohort in research before you make this available to the masses. And it's quite possible that this technique will turn out to be impractical or even harmful when studied at a larger scale. But this is quite a significant result, and a necessary step before going on to study it in more detail.
To get better funding, label grant proposals:
Research for National Defense
The Department of Defense actually sponsors a fair amount of cancer research
posted by grouse at 3:38 PM on August 10, 2011 [1 favorite]
To get better funding, label grant proposals:
Research for National Defense
The Department of Defense actually sponsors a fair amount of cancer research
posted by grouse at 3:38 PM on August 10, 2011 [1 favorite]
The scientific method and I will have to disagree on your definition of "significant result" and "necessary step".
This is a very small safety & efficacy trial analogous to a Phase I trial for a new drug. They are looking to recruit a total of 10 patients, which is about right for this stage. Are you arguing that Phase I trials are unnecessary? Or that their results are not significant (i.e. should have no effect on whether to proceed to Phase II)? You have a very curious definition of "the scientific method" if it disregards medical ethics.
posted by jedicus at 3:53 PM on August 10, 2011 [7 favorites]
This is a very small safety & efficacy trial analogous to a Phase I trial for a new drug. They are looking to recruit a total of 10 patients, which is about right for this stage. Are you arguing that Phase I trials are unnecessary? Or that their results are not significant (i.e. should have no effect on whether to proceed to Phase II)? You have a very curious definition of "the scientific method" if it disregards medical ethics.
posted by jedicus at 3:53 PM on August 10, 2011 [7 favorites]
If you think that, then you don't understand the scientific method. And you don't appear to understand how scientists use the phrase "proof of concept." Proof of concept does not necessarily mean a Phase II clinical trial. The term is used in biomedical sciences all the time and hardly ever to describe a Phase II trial.
As far as "significant," yes, that is a judgment call, but the editors of the New England Journal of Medicine and presumably the peer reviewers disagree with you on that count. Strictly speaking, it's not "necessary" to do a small-scale study like this one before going to a larger one with more statistical value, but for practical reasons it is. Without a study like this, you are very unlikely to get the money to pay for a larger study, the senior personnel to work on it, or institutional review board approval.
posted by grouse at 3:53 PM on August 10, 2011 [6 favorites]
As far as "significant," yes, that is a judgment call, but the editors of the New England Journal of Medicine and presumably the peer reviewers disagree with you on that count. Strictly speaking, it's not "necessary" to do a small-scale study like this one before going to a larger one with more statistical value, but for practical reasons it is. Without a study like this, you are very unlikely to get the money to pay for a larger study, the senior personnel to work on it, or institutional review board approval.
posted by grouse at 3:53 PM on August 10, 2011 [6 favorites]
Hypercritical armchair "scientists" are one of my favorite parts of Metafilter. Surely, we all know better than these dumb researchers! How silly these people with doctorates in their fields must be to make such stupid mistakes that people with absolutely no experience in clinical research can immediately suss them out without even reading the study! Pats on the back all around!
posted by dialetheia at 3:58 PM on August 10, 2011 [17 favorites]
posted by dialetheia at 3:58 PM on August 10, 2011 [17 favorites]
I'm entirely willing to grant that this worked as described.
I think it's terrifying.
The treatment depends on genetically modifying HIV. Which these people will presumably carry for the rest of their lives. Sure, maybe it doesn't screw them over now, but what's to say it won't in ten or twenty years? What's to say it won't enter the population and mutate?
We're like monkeys f*cking with shit we have absolutely no idea how to unf*ck.
Curing two or three people of cancer does not really seem to justify releasing a new form of HIV into the wild.
posted by valkyryn at 4:08 PM on August 10, 2011
I think it's terrifying.
The treatment depends on genetically modifying HIV. Which these people will presumably carry for the rest of their lives. Sure, maybe it doesn't screw them over now, but what's to say it won't in ten or twenty years? What's to say it won't enter the population and mutate?
We're like monkeys f*cking with shit we have absolutely no idea how to unf*ck.
Curing two or three people of cancer does not really seem to justify releasing a new form of HIV into the wild.
posted by valkyryn at 4:08 PM on August 10, 2011
Using a modified, harmless version of HIV, the virus that causes AIDS, they inserted a series of genes into the white blood cells. These were designed to make to cells target and kill the cancer cells.
I think I've seen too many zombie apocalypse movies, because this scares me to death.
posted by bpm140 at 4:23 PM on August 10, 2011
I think I've seen too many zombie apocalypse movies, because this scares me to death.
posted by bpm140 at 4:23 PM on August 10, 2011
The treatment depends on genetically modifying HIV. Which these people will presumably carry for the rest of their lives. Sure, maybe it doesn't screw them over now, but what's to say it won't in ten or twenty years? What's to say it won't enter the population and mutate?
Using an HIV-derived virus for medical treatment is not new or invented for this study. That's something that people have been working on for at least 15 years. I can't say that it is without risk or even that I am a good person to assess the risk, but I will note that it's just like they are just making little changes to HIV. They have removed almost all the HIV genes, including the ones necessary for it to reproduce.
posted by grouse at 4:29 PM on August 10, 2011 [2 favorites]
Using an HIV-derived virus for medical treatment is not new or invented for this study. That's something that people have been working on for at least 15 years. I can't say that it is without risk or even that I am a good person to assess the risk, but I will note that it's just like they are just making little changes to HIV. They have removed almost all the HIV genes, including the ones necessary for it to reproduce.
posted by grouse at 4:29 PM on August 10, 2011 [2 favorites]
A low N can provide significance if the effect size is large enough. That is precisely what is being claimed here, so objecting to it on the basis of a low N is kind of silly. Simply having a low N tells you nothing about the significance of the result.Definitely. People need to understand how statistics work. We didn't need to drop 1000 atomic bombs to know that they would work, we only tested one.
If this treatment cured cancer in one person, we know it can work in theory. That's a statistically significant result. In theory there is a possibility that they spontaneously healed on their own, but that's pretty unlikely.
The fact that they did this on three people and, supposedly, it worked is also relevant.
People whining about how this isn't a 'proper' study don't really understand science as well as they think they do. You have to do tests like this before you do a 'real' trial to make sure it won't kill people (generally, people who have no chance of surviving anyway)
In some cases, it works. There was the article about the guy who was cured of HIV by having a bone marrow transplant, for example. He also had leukemia. He had little chance of surviving, so they decided to try it. It turned out to work in this case.
This is kind of the reverse, using HIV to cure someone with leukemia.
HIV is commonly used to change DNA in human cells. It's used because it's so well studied.
posted by delmoi at 4:41 PM on August 10, 2011 [5 favorites]
The treatment might not be practical in the long term, though. Before any insurance companies pay for it, there will have to be lots more trials and stuff.
posted by delmoi at 4:42 PM on August 10, 2011
posted by delmoi at 4:42 PM on August 10, 2011
a couple of guys in lab coats, sitting around on their coffee break, and one of 'em said, "Hey, I know! What if we sick cancer and AIDS on each other?"
"Hey Dave - Aids vs Cancer - who would win?"
"Ooh... uh... uh... shit, that's a good one. Let's find out!"
posted by -harlequin- at 5:00 PM on August 10, 2011 [2 favorites]
"Hey Dave - Aids vs Cancer - who would win?"
"Ooh... uh... uh... shit, that's a good one. Let's find out!"
posted by -harlequin- at 5:00 PM on August 10, 2011 [2 favorites]
Hard to get funding for cancer research eh? Next weekend I'm taking part in a 240km bike ride to raise funds for cancer research, if anyone feels like sponsoring me I've stuck a link to the online sponsorship page in my profile. Tax deductible if you're in Australia.
posted by markr at 5:27 PM on August 10, 2011
posted by markr at 5:27 PM on August 10, 2011
This is a very small safety & efficacy trial analogous to a Phase I trial for a new drug.
Phase I trials are actually more of the "it works fine in mice, let's make sure it doesn't cause people to sprout new limbs and spontaneously combust." Efficacy testing comes in Phase II. Regardless, 3 subjects with publication on the results of only 1 of them does not a Phase I trial make. This is more like Phase 0.
Although, seeing as how these guys are apparently already getting great results and their subjects are not dropping dead of treatment-related organ failure, combined with the glowing press, I'll bet they've got a good chance of getting some well funded larger studies going. At the very least, the Abramson Lab is going to be sitting pretty the next time the UPenn committee meets.
posted by Panjandrum at 7:05 PM on August 10, 2011
Phase I trials are actually more of the "it works fine in mice, let's make sure it doesn't cause people to sprout new limbs and spontaneously combust." Efficacy testing comes in Phase II. Regardless, 3 subjects with publication on the results of only 1 of them does not a Phase I trial make. This is more like Phase 0.
Although, seeing as how these guys are apparently already getting great results and their subjects are not dropping dead of treatment-related organ failure, combined with the glowing press, I'll bet they've got a good chance of getting some well funded larger studies going. At the very least, the Abramson Lab is going to be sitting pretty the next time the UPenn committee meets.
posted by Panjandrum at 7:05 PM on August 10, 2011
This is total shit.
False hope. Fake science.
Science is based on being able to re-create results.
This is not...and it comes off as "oh its a miracle"...that happened with one person, and 2 that don't want to be known.
Not science, just bullshit in the hopes that we click on their ads and make them money.
Gross.
Hi. I'm a physician-scientist at a tertiary academic center with an advanced degree in research trial design and biomedical statistics. Your description strikes me as incredibly cynical.
The fact that this has yet to be reproduced doesn't mean it is not a potentially incredible scientific achievement.
This required a massive amount of scientific inquiry. You think engineering anti-CD19 specific chimeric antigen receptor modified T cells via a lentivirus is some kind of snake oil potion that was swirled together by chance? This builds on a mountain of work, including data available on the limited success of first generation immunotherapy which failed to yield adequate clonal expansion of memory cell populations without the addition of secondary co-stimulatory domains to the chimeras. The presence of delayed tumor lysis, and complete remission for 10 months under the circumstances described is not a miraculous event that just happened to be coincidental to the infusion of these chimeric cells, which were meticulously monitored by serial flow cytometry and demonstrated 1000-fold increased cell expansion beyond baseline. Unless the report is outright lying (which I grant is possible), and images from CT scans and bone marrow slides are fabricated, this is a remarkable scientific accomplishment in the put-a-man-on-the-moon or create-a-sustained-fusion-reaction or successfully-transplant-an-organ-for-the-first-time sense. Case reports don't just get published in NEJM, unless they are so.
It may not be a cure for cancer or even a fraction of cases of CLL, but it most certainly has lead to durable complete remission in at least one patient, which is remarkable, and serves as proof-of-concept for an entirely new paradigm of treatment for a wide variety of conditions.
You really believe this is best described as "total shit"? You think the tenured directors of bone marrow transplantation and translational research at UPENN, with over 300 publications under their belt, are just desperately trying to make a buck here?
posted by drpynchon at 8:26 PM on August 10, 2011 [34 favorites]
False hope. Fake science.
Science is based on being able to re-create results.
This is not...and it comes off as "oh its a miracle"...that happened with one person, and 2 that don't want to be known.
Not science, just bullshit in the hopes that we click on their ads and make them money.
Gross.
Hi. I'm a physician-scientist at a tertiary academic center with an advanced degree in research trial design and biomedical statistics. Your description strikes me as incredibly cynical.
The fact that this has yet to be reproduced doesn't mean it is not a potentially incredible scientific achievement.
This required a massive amount of scientific inquiry. You think engineering anti-CD19 specific chimeric antigen receptor modified T cells via a lentivirus is some kind of snake oil potion that was swirled together by chance? This builds on a mountain of work, including data available on the limited success of first generation immunotherapy which failed to yield adequate clonal expansion of memory cell populations without the addition of secondary co-stimulatory domains to the chimeras. The presence of delayed tumor lysis, and complete remission for 10 months under the circumstances described is not a miraculous event that just happened to be coincidental to the infusion of these chimeric cells, which were meticulously monitored by serial flow cytometry and demonstrated 1000-fold increased cell expansion beyond baseline. Unless the report is outright lying (which I grant is possible), and images from CT scans and bone marrow slides are fabricated, this is a remarkable scientific accomplishment in the put-a-man-on-the-moon or create-a-sustained-fusion-reaction or successfully-transplant-an-organ-for-the-first-time sense. Case reports don't just get published in NEJM, unless they are so.
It may not be a cure for cancer or even a fraction of cases of CLL, but it most certainly has lead to durable complete remission in at least one patient, which is remarkable, and serves as proof-of-concept for an entirely new paradigm of treatment for a wide variety of conditions.
You really believe this is best described as "total shit"? You think the tenured directors of bone marrow transplantation and translational research at UPENN, with over 300 publications under their belt, are just desperately trying to make a buck here?
posted by drpynchon at 8:26 PM on August 10, 2011 [34 favorites]
Hal, nobody is saying this should be rolled out and made available to millions of leukemia patients. All this study shows is that this novel approach does seem to have been effective in these few cases. That's it.
It's the groundwork for a larger study, and as I said before, this is what well-documented, meticulously planned, and methodologically sound case study research does well.
posted by yellowcandy at 9:45 PM on August 10, 2011 [2 favorites]
It's the groundwork for a larger study, and as I said before, this is what well-documented, meticulously planned, and methodologically sound case study research does well.
posted by yellowcandy at 9:45 PM on August 10, 2011 [2 favorites]
Regardless, 3 subjects with publication on the results of only 1 of them does not a Phase I trial make
The study is recruiting 10 patients, as mentioned and linked above. They just reported some early highly positive results.
posted by jedicus at 10:00 PM on August 10, 2011
The study is recruiting 10 patients, as mentioned and linked above. They just reported some early highly positive results.
posted by jedicus at 10:00 PM on August 10, 2011
I have issue with the author being interviewed by MSNBC and presenting it as a cure of cancer...and the ONLY thing stopping him from curing the world is money. I mean everyone knows this altruistic and highly unambitious doctor just wants to advance science...its just that he needs money to do it.
Carl June does not appear to present it as a cure for cancer in the MSNBC article. I don't know where you're getting that from.
Yes, it costs money to run research studies, especially medical studies on human patients. You have to pay the staff that work with these patients, the staff that perform laboratory work, and the staff that perform support services. You have to pay for necessary reagents and equipment. You have to pay a company to make the vector for you (or pay for staff, reagents, and equipment to do it yourself, which will likely be more expensive and take longer).
You can tell because it says harvard on his wall.
June didn't go to Harvard. Now you're just making things up.
posted by grouse at 10:32 PM on August 10, 2011
Carl June does not appear to present it as a cure for cancer in the MSNBC article. I don't know where you're getting that from.
Yes, it costs money to run research studies, especially medical studies on human patients. You have to pay the staff that work with these patients, the staff that perform laboratory work, and the staff that perform support services. You have to pay for necessary reagents and equipment. You have to pay a company to make the vector for you (or pay for staff, reagents, and equipment to do it yourself, which will likely be more expensive and take longer).
You can tell because it says harvard on his wall.
June didn't go to Harvard. Now you're just making things up.
posted by grouse at 10:32 PM on August 10, 2011
This reads pretty much like proper science to me. It's a darn small sample, but if they really have 3/3 patients with significant response, it is pretty promising news.
Things to note:
-CLL has slow growth and long remissions. 1 year without progression is not a very long time in CLL land. (Although it is excellent)
-This is research that builds on somewhat congruent treatments. It is based on CD19 sensitivity. Existing drugs (Zevalin, rituximab) work on CD20 sensitivity. It's not like they are selling shark cartilage or something.
I work with a number of CLL patients in stem cell transplant. And although I like my job, it is not a great treatment for most of these people. All hype aside, this study is exciting.
posted by SLC Mom at 10:38 PM on August 10, 2011
Things to note:
-CLL has slow growth and long remissions. 1 year without progression is not a very long time in CLL land. (Although it is excellent)
-This is research that builds on somewhat congruent treatments. It is based on CD19 sensitivity. Existing drugs (Zevalin, rituximab) work on CD20 sensitivity. It's not like they are selling shark cartilage or something.
I work with a number of CLL patients in stem cell transplant. And although I like my job, it is not a great treatment for most of these people. All hype aside, this study is exciting.
posted by SLC Mom at 10:38 PM on August 10, 2011
I mean everyone knows this altruistic and highly unambitious doctor just wants to advance science...its just that he needs money to do it.
Yeah, how strange is THAT? It's like they're saying that advancing human knowledge requires resources. Instead, they can all just sit around in their spare time praying about it; that's much cheaper.
posted by Philosopher Dirtbike at 12:18 AM on August 11, 2011
Yeah, how strange is THAT? It's like they're saying that advancing human knowledge requires resources. Instead, they can all just sit around in their spare time praying about it; that's much cheaper.
posted by Philosopher Dirtbike at 12:18 AM on August 11, 2011
From an earlier report:
"... by the second day of incubation, any cells that have undergone reversion mutations give rise to revertant colonies like rats leaving a sinking ship; then the ship sinks. With EMS recombination, ethyl methane sulfonate is an alkylating agent and a potent mutagen. It created a virus so lethal the subject was dead before he left the table. A repressor protein that blocks the operating cells wouldn't obstruct replication, but it does give rise to an error in replication so that the newly formed DNA strand carries a mutation and you've got a virus again.
But this - all of this is academic."
posted by Devonian at 1:04 AM on August 11, 2011
"... by the second day of incubation, any cells that have undergone reversion mutations give rise to revertant colonies like rats leaving a sinking ship; then the ship sinks. With EMS recombination, ethyl methane sulfonate is an alkylating agent and a potent mutagen. It created a virus so lethal the subject was dead before he left the table. A repressor protein that blocks the operating cells wouldn't obstruct replication, but it does give rise to an error in replication so that the newly formed DNA strand carries a mutation and you've got a virus again.
But this - all of this is academic."
posted by Devonian at 1:04 AM on August 11, 2011
"Hey, I know! What if we sick [sic] cancer and AIDS on each other?"
I couldn't resist.
posted by Deathalicious at 6:25 AM on August 11, 2011 [1 favorite]
I couldn't resist.
posted by Deathalicious at 6:25 AM on August 11, 2011 [1 favorite]
The treatment depends on genetically modifying HIV. Which these people will presumably carry for the rest of their lives. Sure, maybe it doesn't screw them over now, but what's to say it won't in ten or twenty years? What's to say it won't enter the population and mutate?
Oh, come on. If the movies have taught us anything, it's that taking dangerous things and modifying their DNA -- especially for medical purposes -- is completely safe and does not at all require the services of an only semi-literate action hero who survives along with his new hot girlfriend while all the scientists are slowly but surely picked off like flies.
posted by Deathalicious at 6:30 AM on August 11, 2011
Oh, come on. If the movies have taught us anything, it's that taking dangerous things and modifying their DNA -- especially for medical purposes -- is completely safe and does not at all require the services of an only semi-literate action hero who survives along with his new hot girlfriend while all the scientists are slowly but surely picked off like flies.
posted by Deathalicious at 6:30 AM on August 11, 2011
"And THOSE are the responses this research is meant to illicit from the public."
elicit
posted by Eideteker at 7:31 AM on August 11, 2011
elicit
posted by Eideteker at 7:31 AM on August 11, 2011
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