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Medicine

Altered Immune Cells Help Girl Beat Leukemia 130

An anonymous reader writes "For decades, one of cancer's most powerful weapons has been to corrupt the human immune system. Finally, researchers in Philadelphia have developed a way to turn that weapon against certain cancers, and potentially open the door to a whole new generation of therapies for all manner of cancers. From the article: 'It is hard to believe, but last spring Emma, then 6, was near death from leukemia. She had relapsed twice after chemotherapy, and doctors had run out of options. Desperate to save her, her parents sought an experimental treatment at the Children’s Hospital of Philadelphia, one that had never before been tried in a child, or in anyone with the type of leukemia Emma had. The experiment, in April, used a disabled form of the virus that causes AIDS to reprogram Emma’s immune system genetically to kill cancer cells.'"
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Altered Immune Cells Help Girl Beat Leukemia

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  • Really; it sounds wonderful, but if Murphy and Pandora had a child, his/her favorite toy would be using lethal viruses to help us combat lethal cancers.

    Using nuclear weapons to plug oil gushers, using attack polar bears to guard your bunny farm, using a scalpel to pick your nose... these ideas will go right some of the time too.

    A link with more detail:
    http://www.telegraph.co.uk/health/healthnews/9508895/A-virus-that-kills-cancer-the-cure-thats-waiting-in-the-coldc.html [telegraph.co.uk]

    • by RearNakedChoke ( 1102093 ) on Monday December 10, 2012 @06:09PM (#42246513)
      A virus is not lethal. It is merely a vehicle, a means of reprogramming cells. Its hardware. The lethality is in the software.
      • by jamesh ( 87723 )

        A virus is not lethal. It is merely a vehicle, a means of reprogramming cells. Its hardware. The lethality is in the software.

        I don't see how you can reach that conclusion. A virus is almost pure software.

        • A virus is not lethal. It is merely a vehicle, a means of reprogramming cells. Its hardware. The lethality is in the software.

          I don't see how you can reach that conclusion. A virus is almost pure software.

          A virus is pure intangible idea/algorithm/concept/instruction? Granted its been a few years since I took biology, but I'm pretty sure all viruses have some sort of outer layer/covering, with their "software" encoded using RNA inside. That's pretty cut and dry hardware and software to me...

          • by Tmann72 ( 2473512 ) on Monday December 10, 2012 @06:38PM (#42246797)
            Not just that, but the Virus's physical form is simply a payload mechanism to inject the virus genetic code into healthy cells. The healthy cell that was infected now becomes a virus factory creating tons of new virus cells until it explodes releasing them into your system. There is a very cut and dry hardware to software paradigm here. If we consider that a virus is nothing but a genetic delivery mechanism it instantly becomes the greatest tool humanity has for this type of work. Nothing we can currently create would be even a fraction as effective.
        • By that logic human bodies are entirely software as well, but that obviously isn't correct. Our DNA was used to create our entire body inside of our mothers similar to how the RNA in a virus is used to turn a cell into a virus factory. The maturation chamber and injection mechanisms differ, but the RNA, and DNA in both instances completely describes the physical form to be created. However, once formed there is a very distinct permanency to the physical body that makes it hardware and not software. It conta
      • Re: (Score:2, Insightful)

        by Nyder ( 754090 )

        A virus is not lethal. It is merely a vehicle, a means of reprogramming cells. Its hardware. The lethality is in the software.

        In other words, viruses don't kill people, people kill people.

      • That definition is misleading. In general medical usage, 'virus' actually describes a collection of several different aspects: the software, hardware, and the behaviour of the software when run. The term 'virus particle' or 'virion' is closer to what you intend, although due to synecdoche the summary is not mistaken when it uses the term "reprogrammed virus" to refer to engineered viral particles.
    • The problem is... our immune systems are a lot better equipped to deal with viruses than with cancer. Think about it, to kill cancer, your symptoms are similar to a cold. If this takes off, remember all those years they spent trying to treat it with drugs? They've made some progress, but it's relatively insignificant in comparison to a cure. Your body's body is it's best friend :)
    • by Anonymous Coward on Monday December 10, 2012 @06:12PM (#42246531)

      using lethal viruses to help us combat lethal cancers.

      Big deal. Lots of things useful things are lethal. Hell, I was injected with a disabled lethal virus a couple weeks ago. Just in time to keep me from being part of this year's flu season. Pretty much every cancer treatment kills things. That's how they work. The goal is to kill the cancer without killing too much of the person with it.

    • by TWX ( 665546 )
      On the other hand, it takes a fair amount of effort or some very specific actions to transmit HIV, and while this may well cause problems for this girl's life post-adolescence, she'll live to reach it.
    • by Picass0 ( 147474 ) on Monday December 10, 2012 @06:13PM (#42246545) Homepage Journal

      While I understand your concerns, every medical breakthrough has involved risk.

      The polio vaccine could have backfired, but it didn't. You and I have grown up without the fear of a disease that plagued every generation up to our parents.

      • by Art Popp ( 29075 ) *

        A fair point. There is a very real price to be paid, in the lives of innocent kids, by not boldly exploring this terrain.

        My primary worry is that people are so desperate for this cure, so desperate to focus on something hopeful, that it will become a primary technique before it's long term consequences are well understood. Thalidomide is a great drug for a very narrow range of problems. When applied to morning sickness an estimated 10,000 children in 46 countries got to live with deformities.

        My hope is t

        • by Picass0 ( 147474 )

          I also hope ethic medical testing is conducted. That said, most of us know (or have known) someone with a terminal illness. If that person were given a chance to alter a certain outcome by using cutting edge medicine most would jump on it.

          • Yes, ethical testing would include people who are desperate and willing to try it. A frayed rope is better than nothing if you're falling.
            My best friend is in that position, and would certainly jump at the opportunity to aid research by either staying alive himself, or helping someone else in his position down the track.

        • My hope is that the companies who stand to profit from this test very thoroughly on a large batch of patients for many years.

          They're called "Phase III clinical trials" in the US, and they are absolutely mandatory for obtaining FDA approval to market the product, and effectively mandatory if you want insurance companies to reimburse, without which the market would be prohibitively small. But even the best-run large-scale clinical trial, where every adverse effect is cataloged and reported, won't always catc

    • by MozeeToby ( 1163751 ) on Monday December 10, 2012 @06:23PM (#42246631)

      Your link isn't the same research as what the article is talking about though.

      The article is about removing a patient's stem cells, using neutered HIV to deliver a payload to them that changes the immune system at a genetic level and then reintroducing the stem cells into the patient. The patient's immune system would then be equipped to kill the cancer. Your link discusses infecting patients with a virus that targets cancer cells preferentially, killing a cancer while at the same time giving the patient only mild symptoms.

      On the one had, the article is talking about real, honest to goodness genetic engineering of a living human being which is, quite frankly, science fiction levels of amazing. But it almost universally causes a cytokinetic swarm in the patient as the immune system suddenly knows how to fight massive amounts of what it suddenly sees as infected tissue (actually tumors). The HIV is disabled the same way other viruses are disabled to create vaccines, and even if the patient got HIV somehow that would in fact still be preferable than dying immediately from cancer.

      On the other, your article would indicate a cure that would be essentially zero cost to produce. The side affects are minimal but, and this is the proverbial "but" that is probably killing all research on the topic, you also have a virus that is capable of killing the vast majority of one tissue type (tumor) inside the human body. And that is quite frankly terrifying. Until you can quantify how likely or unlikely the virus is to target a different tissue type and how likely is it that the virus is communicable (or could mutate to become so) you won't be trying it out on anyone.

      • by Art Popp ( 29075 ) *

        Thank you MozeeToby. I thought the difference in these solutions was more confined to the delivery mechanism, but they appear to be more distinct. Yes, it's the "selective tissue killer virus" version that seems far more problem-ready to me too.

        If the only place the T-cells get modified is in a test tube, and the only modified T-cells the patient gets are from the doctor, and the patients are not the test-tube in which this combining takes place.... Then I find it much less forboding.

    • by Anonymous Coward
      Cars are dangerous, but it's extremely difficult to run somebody over with a car that has no axles. Just as axles are required to move a car under its own power parts of HIV have been removed so that it cannot replicate (and then cause and transmit AIDS) on its own.
    • by kwyjibo87 ( 2792329 ) on Monday December 10, 2012 @06:35PM (#42246767)

      "[using] a disabled form of the virus that causes AIDS"

      While true, this is a poor way to describe a lentiviral vector, meant to invoke the idea of using HIV to kill cancer in the minds of readers not familiar with modern molecular biology. HIV is a type of virus called a lentivirus, which itself is a type of retrovirus, which means that it takes the RNA genetic code it has packaged in the virion, chemically transforms it into DNA, and integrates this DNA into the DNA of the infected cell. Lentiviral vectors are designed such that they do this part of the viral life cycle, but are engineered to lack the genes necessary to make more viruses, so the integrated virus is dead on arrival.

      In this case, the researchers kept the normal HIV surface receptors so the virus would efficiently target and "infect" T-cells from the patient; normally, lentiviruses are given a generic non-HIV receptor so they can infect any cell type you might be using in your lab experiments. The lentivirus genome contained not the normal viral genes, but a chimeric T-cell receptor designed to stimulate an immune response against CD-19, a surface protein specific to B-cells. Once this chimeric gene is integrated, the T-cells will express it on their cell surface, and stimulate the immune system to target and destroy cells that have CD-19 on them; this kills all the B-cells in the body, both healthy and cancerous. This last point is a problem brought up by TFA, that the patient now essentially has a limited auto-immune disorder as the altered T-cells persist in her body and continue to point them immune system to targeting B-cells, leaving her partially immuno-compromised (which is the funny part about using the "virus that causes AIDS" to do this).

      • by EuNao ( 1653733 )

        It would be amazing if they could change this technology so that it was activated by the presence of some environmental activation molecule (maybe a not so common antibotic would be a good choice.) This technique has great promise, if we could only turn it off and on at will. Perhaps the cytokine storm could be alleviated if you could somehow ramp the response up by concentration of the drug, instead of the current 'nuclear' level immune response.

        Very f'ing awesome stuff, as a kid I toyed with the idea o

      • So the new altered T cells can reproduce themselves? How hard would it be to have nerfed ones with limited lifespans and no ability to reproduce?
    • by amiga3D ( 567632 )

      I think as a last desperate attempt it makes sense. If the patient is dying then why not try it? Worst case? They die anyway.

    • by Anonymous Coward

      Really; it sounds wonderful, but if Murphy and Pandora had a child, his/her favorite toy would be using lethal viruses to help us combat lethal cancers.

      Using nuclear weapons to plug oil gushers, using attack polar bears to guard your bunny farm, using a scalpel to pick your nose... these ideas will go right some of the time too.

      A link with more detail:
      http://www.telegraph.co.uk/health/healthnews/9508895/A-virus-that-kills-cancer-the-cure-thats-waiting-in-the-coldc.html [telegraph.co.uk]

      You'd rather watch your 6-year-old child die before your eyes?

      I'm glad you're not my parent.

    • by epp_b ( 944299 )
      Huh, I didn't detect even a hint of sarcasm there. It's like you're unaware that chemotherapy is actually poison pumped directly into the bloodstream.
  • by kc9jud ( 1863822 ) on Monday December 10, 2012 @06:03PM (#42246473)
    • by Guppy ( 12314 ) on Monday December 10, 2012 @07:30PM (#42247161)

      I am not a doctor, but I am a med student. :)

      Historically, our techniques for treating cancer can be categorized into three categories: chemotherapeutics/radiation which attack rapidly dividing cells indiscriminately; "magic bullet" chemotherapeutics which exploit specific quirks of a cancer's biology -- a feature that differentiates it from normal cells (the perfect solution, but far too few such exploits are known); and immuno-therapeutics that utilize the body's own defenses. In practice, many techniques combine some aspects from the different approaches.

      The immuno-therapeutic approach has a long history, beginning with Coley's Toxins [wikipedia.org], and there are a few cases where a cancer is naturally immunogenic enough for it to work (for instance, using BCG to evoke a response to certain kinds of bladder cancer). It has been hypothesized that the immune system eliminates most abnormal cells before they become cancerous, but the flip-side of this hypothesis, is that abnormal lineages which do become cancers, would only be able to do so because they gained mutations allowing them to evade or suppress that normal defense. In addition, while certain types of cancer increase in frequency in populations with long-term immune suppression (due to AIDS, organ transplant drugs, or some other acquired or congenital condition), many other types of cancer do not -- suggesting that in those cancer types, the immune system's normal tendency to avoid attacking the self, may alone be sufficient to shield them.

      Anyway, what is particularly impressive about this CAR-T (Chimeric Antigen Receptors T-Cell) technique, that has been generating a lot of excitement, is its ability to completely and permanently break immune tolerance -- to the point where it does not need to target some identifiable abnormal feature of the cancer, but can target a completely normal feature of that cancer cell's lineage. In this case, the normal CD-19 receptor is targeted, and results in the entire population of B-Cells being wiped out. The leukemia is a sub-set of this cell population, so it is eliminated as well, with the bonus of a persistent immune response that continually suppresses any survivors. The downside is that the patient is left with no B-Cells to produce antibodies, and thus relies on periodic infusions of IVIG (Intravenous Immunoglobulin, consisting of antibodies pooled from donors) to protect against infection.

      • What's the end game for this type of treatment; we always balance wiping out an entire class of genes or...?

        Also, what do they call the nanobot swarm treatment? :)

        • by Guppy ( 12314 ) on Tuesday December 11, 2012 @12:03PM (#42251059)

          What's the end game for this type of treatment

          It's hard to say, but there's much potential here. Next antigen targets on their list [upenn.edu] include MAGE-A3 (melanomas, and some lung and other cancers), NY-ESO-1 (some testicular and other cancers), and Mesothelin (mesothelioma, and some ovarian and pancreatic cancers).

          It may also be possible to apply this technique to some diseases other than cancer -- AIDS is on the list as well. While HIV normally generates a robust (but ultimately futile) immune response, it may be possible to enhance that normal defense, by using this technique to direct it into a more cell-mediated (as opposed to humoral) response, and also engineering the modfied T-cells to be resistant to HIV infection.

      • , with the bonus of a persistent immune response that continually suppresses any survivors. The downside is that the patient is left with no B-Cells to produce antibodies, and thus relies on periodic infusions of IVIG

        Is there some thought that the patient's marrow is going to continue to produce cancerous B-cells? It seems that way because otherwise they'd produce a killer-T-cell with a terminator gene, right?

        • by Guppy ( 12314 )

          Is there some thought that the patient's marrow is going to continue to produce cancerous B-cells? It seems that way because otherwise they'd produce a killer-T-cell with a terminator gene, right?

          The research group involved has stated they would like to try including a self-destruct mechanism in their modified cells, but they're taking it one step at a time. And, it may very well be that the leukemia is being produced by a "cancer stem cell" that escapes targeting by this approach, or that there are surviving leukemia cells present at a low level. We don't know yet.

    • You know that classifies as FUD, right?
  • AIDS vs. Cancer (Score:2, Interesting)

    If it turns out that the AIDS virus took 50 years off of the timeline to finding a cure for cancer, I wonder if the AIDS epidemic was worth it.

    • It was to me, but I didn't die from aids, nor did anyone I knew.

      • Re:AIDS vs. Cancer (Score:5, Insightful)

        by Nyder ( 754090 ) on Monday December 10, 2012 @06:37PM (#42246783) Journal

        It was to me, but I didn't die from aids, nor did anyone I knew.

        My neighbor, who had AIDS, died a week ago.

        While this doesn't matter to you (it's cool.), it does show that AIDS still affects people and others around people with AIDS.

        He ended up with cancer in his bone marrow, was given kemo, but when told he wasn't going to be able to go home again (would require 24 care which he couldn't afford), he chose to stop taking treatments, and died a couple days later. And I don't blame him.

        So even it AIDS virus took 50 years off the timeline to finding a cure for cancer, it doesn't matter to my neighbor, because he's dead regardless. But I think he'd be happy to know that even while AIDS was bad for him, it might be doing some good for others.

        • Hold up, I know that AIDS can result in cancer .. but in his case did he really die of AIDS or did he die of a bone marrow cancer that originated regardless of his HIV infection? I mean it's possible that the cancer progressed due to a low immune cell count .. but if he was on his meds that shouldn't have happened .. unless of course he found out he had HIV after or around the time he got cancer due to a low T-cell count. Or, his HIV was resistant to all drugs .. which is not unheard of but rare.

    • HIV isn't the only retrovirus or the only virus that targets T-cells. I will admit that the crisis that AIDS has posed has greatly accelerated research into retroviruses, but the development of retroviruses as gene therapy vectors is only tangentially connected to research on AIDS as a disease.

      AIDS as a pandemic has from the start been as much or more about public health measures as it has virology, and if we had been far more fortunate, HIV would have remained a fearsome but rare curiosity. Research on it

  • Jared: "I lost weight because I got aids, and I want to give everyone Aids too!"

    But seriously its extremely cool to see the sci-fi like ideas that you watch and just think "yea right" come to life. One could almost argue that the vision of art helps drive the dream of science. Maybe what the US Government needs to invest in rather than a huge boondoggle bill is a new Star Trek trilogy!
  • by Thud457 ( 234763 ) on Monday December 10, 2012 @06:26PM (#42246681) Homepage Journal
    Will Smith thinks this is a bad idea.
  • Knee Jerk (Score:5, Informative)

    by headhot ( 137860 ) on Monday December 10, 2012 @06:36PM (#42246773) Homepage

    Wow there are a lot of people freaking out they are using HIV for this.

    Um, relax, they didn't give the girl HIV, they re-engineered the virus into something new. The virus doesn't replicate in the to host. T-cells removed from the host are exposed to the engineered HIV. The engineered HIV then changes the DNA in the T-cells to allow it to attack cancerous B-cells. The T-cells are then re-injected and do their work. The T-cells continue to replicate, but the engineered HIV is not actually introduced into the body.

    • Re:Knee Jerk (Score:5, Informative)

      by Kyusaku Natsume ( 1098 ) on Monday December 10, 2012 @07:15PM (#42247071)

      I would mod you up to 11. The drawback, aside the initial cytokine storm is the complete loss of B-cells. I suppose that they could store unaltered T-cells and return the unaltered T-cells after they confirmed cancer remission, in a tick-tock strategy to let the patient recover their healthy B-cells. HIV is only a vehicle, in the same vein a pill is a vehicle for medicine, nothing else.

    • Re:Knee Jerk (Score:4, Informative)

      by Turminder Xuss ( 2726733 ) on Monday December 10, 2012 @09:25PM (#42248021)
      Exactly and thankyou. It's like amputating the B-cells. Not a risk free procedure, the cytokine storm can kill and then the resultant immune deficiency effects must be managed. But a susceptibility to colds is a lot better than leukemia. The treatment targets all B-cells, whether cancerous or not. We are still not identifying and destroying cancerous cells only. That is when words like "cure" might get to be used.
  • by Bacon Bits ( 926911 ) on Monday December 10, 2012 @06:59PM (#42246979)

    My mother was diagnosed with acute myelodysplastic syndrome in 2006, and the doctors she spoke with talked about this type of treatment. At the time it was not ready for use in humans, however. We did talk for awhile with the doctors about the nature of cancer and this type of treatment.

    Many people are aware that cancer is present in almost all people at several times in their lives. The vast majority of cancers are from genetic defects that the body detects as an alien, and it will attack and destroy the mutated cells just as foreign bacteria or a transplanted organ are. Now, the types of cancer that we talk about and that result in terminal illness is from a mutation that is different enough to be deadly and parasitic to the human body, but not different enough to be detected as different.

    All cells contain markers that act as identification badges. Last I was aware, there were 10 known genetic markers for humans that determine this identity (only six were known in the 1990's, so this is pretty new stuff). Its these markers that are used to find organ and tissue donors. However, even a perfect 10 out of 10 match is not enough to guarantee that foreign tissue will be detected as alien, so we know that our known list of 10 markers is incomplete. This is why perfect matches still face rejection risks.

    The problem then, from a leukemia perspective, is that donor bone marrow will produce white blood cells that see the recipient body as alien, and attack it. That's kind of what you want, since the idea is to kill the cancerous bone marrow, but it's not exactly discriminate about what it will attack. So for leukemia treatment, you don't even want a perfect 10 out of 10 match since that would be counterproductive. Perfect donor bone marrow wouldn't identify the cancer either, and the cancer would relapse.

    What this treatment does is gives doctors a way to tell your body that certain cells are aliens by forcefully altering their DNA. Then the body can just fix itself. That's really what medicine does best: allows the body time to fix itself.

    "How can this possibly work?" you think. "Aren't all cancers different?" Well, it turns out the answer is "sort of". We categorize cancers based on the kind of tissue that is affected, but that's really not accurate. We should categorize it based on exactly what genetic sequence mutated and in exactly what way. Cancer, then, is literally a family of thousands of diseases with very similar symptoms. Many cancer types are, in fact, mutations of the same segment in the same way. However, now that we are able to sequence the DNA of a human, we ought to be able to accurately categorize each person's individual cancer by sequencing healthy and cancerous cells. We can then design a DNA segment which will only work in the DNA sequence of cancerous cells and that will identify the cells as alien to the body. The body will then attack the cancer, and destroy it. We will, literally, paint a target on the cancer cells for the human body to destroy. The mechanism for delivery of this kind of genetic manipulation is already supplied to us by nature in the form of a retrovirus. In this girl's case, the retrovirus that seeks out her cancerous cell type is HIV, which attacks white blood cells.

    This, then, is the most promising path to the cure for cancer. It will not be cured with a single treatment like polio or smallpox, but the method can be applied over and over against every type of cancer.

    My mother was given more traditional treatment with a bone marrow transplant. The best match that could be identified was an 8 out of 10 match. Even so she successfully underwent the transplant and survived a year longer than she was given when diagnosed. She then relapsed, and was beginning her second treatment when she died from a massive stroke caused by all the medications required to treat the disease and the anti-rejection drugs and the side effects of the medications. If she had had this kind of option where doctors could reprogram her immune system to seek and destroy the cancerous bone marrow like it's supposed to instead of having to rely on grafted bone marrow that would attack her healthy tissue as well, she might still be alive today.

    • Re: (Score:3, Interesting)

      by Anonymous Coward

      So for leukemia treatment, you don't even want a perfect 10 out of 10 match since that would be counterproductive. Perfect donor bone marrow wouldn't identify the cancer either, and the cancer would relapse.

      Actually, that's not automatically true.

      My youngest son developed Acute Myelogenous Leukemia when he was 18 months. He underwent chemo for six months and went into remission. Eight months later he relapsed, so the doctors told us that the next step was a bone marrow transplant. To have peace of mind that we were doing all we could to save him, my wife insisted that she and I get tested for donor compatibility even though the odds of a parent being an acceptable donor are infinitesimal. The donor and patient

    • In this girl's case, the retrovirus that seeks out her cancerous cell type is HIV, which attacks white blood cells.

      Not to detract from your post, but I have to be picky about this.

      This girl had T-cells removed from her body. Then reprogrammed HIV cells were used to patch the T-cell code so that it would target B-cells. Then the patched T-cells were injected back into her. At no point in time was she exposed to the virus.

    • Targeting a single DNA segment is unlikely to work in most cases if the cancer has reached stage IV. The problem is the mutation rate in most cancers especially if the oncogene wasn't specifically inherited is scary high ( http://www.ncbi.nlm.nih.gov/pubmed/19931353 [nih.gov] ) .. cancers contain cells with not just SNP mutations but all kinds of copy variants .. frame shifts etc.. To get a high confidence of eradicating the tumor .. honestly after looking at the myriad of different mutations and amount of cell to ce

  • In case you're thinking "yeah, cancer, big deal. People die every day" I welcome you to watch Anthony Griffith on The Moth [youtube.com] describe his personal experience with leukemia.

    WARNING: NSFW -- both for (IIRC) some rather strong language and the uncontrollable weeping that will consume you for the rest of the day.

  • But when we're all huddled into a dark building hoping Dr. Carl "Legend" June doesn't drag us off for use in bizarre medical experiments to cure the plague he ended up accidentally creating, will you still think this is a good idea?

What is research but a blind date with knowledge? -- Will Harvey

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