Gene Therapy Brings Three Cancer Patients Back From Death's Door; What Now?

By Veronique Greenwood | August 11, 2011 3:06 pm

Modified immune cells decimated chronic lymphocytic leukemia, scientists found.

What’s the News: Striking results in a very small study have got the web a-buzz about a new cancer treatment: With three leukemia patients at the ends of their ropes, scientists modified some of their immune cells with a gene that enabled them to hunt down cancer cells. Remarkably, the treatment wiped out more than two pounds of tumor tissue in each patient, and the three have now been in remission for a year.

But what weight does such a small study carry, what about the side effects, and what do these results mean for people with other cancers?

How the Heck:

  • First, the team removed immune cells called T cells from each of the patients, who had chronic lymphocytic leukemia, a cancer affecting blood cells called B cells.
  • They had a lab-built virus insert a gene for a protein that would recognize a specific tag appearing only on the surface of B cells, as well as genes for two other proteins involved in the process, into the T cells. (This kind of treatment, called gene therapy, has been of interest in treating cancer for some time.)
  • The team then injected each patient’s own T cells back into their blood, where they began attacking the cancer cells, whose death the team confirmed with blood tests and other measurements.
  • Taking counts of the patients’ cells, they estimate that each modified T cell must have hunted down and killed a thousand cancer cells. Before the treatment, the ratio of cancer cells to normal cells in the bone marrow was horrifying: in one patient, 170 out of 200 were cancerous. Afterwards, that number was only 2 out of 200.
  • The modified T cells have remained in the patients, even months after the treatment, potentially contributing to the patients’ ongoing remission.

Not So Fast:

  • Cancer patients are routinely exposed to treatments much worse, at least in the short term, than the disease: killing cancer cells means killing a lot of healthy cells. With this treatment, nearly all of the patients’ B cells, healthy and otherwise, were destroyed, and even months afterwards the B cells had not recovered. Since this is the class of immune cells that produces antibodies, this loss could be quite serious in the long term, though all the rest of the patients’ cells were unharmed.
  • The team also notes that the mass murder of cancer cells provoked a serious response: the patients’ bodies were flooded with detritus from the bursting cells and inflammatory molecules produced by the immune system, some at 160 times the normal levels. Their kidneys were in acute distress, and at least one had to be hospitalized because of it. The researchers note that they are really going to have to pay attention to this when they’re designing larger studies. Maybe the injections will be spread out more, or maybe not as many altered immune cells are required.
  • Additionally, one of the most exciting things about this study—that the T cells stay in circulation and may keep destroying any cancer that crops up for years—makes it quite different from, and possibly riskier than, most cancer treatments, which usually are purged from your body in a matter of weeks. That means that the follow-up work to figure out what the T cells are doing, and whether they might be somehow dangerous in the long term, will be substantial. What, for instance, will the indefinite lack of B cells mean? The FDA will need serious reassurance on these points, especially since gene therapy carries a risk of causing mutations in modified cells that might eventually turn them cancerous over the patient’s lifetime.

The Future Holds:

  • The next step for the researchers is much, much larger studies, incorporating the points raised above. For all intents and purposes, this report is a case study, without the statistical power required for assessing a treatment’s usefulness in the population at large.
  • Researchers who focus on other cancers may also find it difficult to translate this success to their own patients: this team was able to make this work because they knew exactly what surface protein to target. As they point out in their report, we don’t have analogous information for many other cancers. And ideally, we’d find proteins that are specific to the cancer, not to the cell type, to avoid the problem this team is facing with B cells. So get cracking, all you budding researchers!

References: Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia. David L. Porter, M.D., Bruce L. Levine, Ph.D., Michael Kalos, Ph.D., Adam Bagg, M.D., and Carl H. June, M.D. New England Journal of Medicine, August 10, 2011 (10.1056/NEJMoa1103849).

T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia. Michael Kalos, Bruce L. Levine, David L. Porter, Sharyn Katz, Stephan A. Grupp, Adam Bagg and Carl H. June Sci Transl Med 10 August 2011: Vol. 3, Issue 95, p. 95ra73. DOI: 10.1126/scitranslmed.3002842

Image credit: Wikimedia Commons

CATEGORIZED UNDER: Health & Medicine, Top Posts
  • anthony smith-porter

    wow that sounds amazing NOT!!!!!!!!!!!!!!!!!!!!

    Has anyone given the time to look more carefully at this T-Cell. I mean come on no one in their right mind can be so stupid to believe that after this t-Cell kills the cancer it will magically go away. NO! when something is sent to do a job it will do it until it is complete. And these T-Cell are made to kill the threats to the immunity system .
    And yes i know your thinking that it was just made to destroy cancer but nothing in medical history has been made to do one thing and has done that one thing and gone away. No. There’s always a side effect, and i can tell you that the side effects for this T-Cell experiment done on these three men will have some very catastrophic side effects. As someone who is studying the medical field i can see these issues coming up and this is my first year. i would take a completely different approach. Thank you

  • Saige

    There wasn’t anything in this report suggesting that the patients were men.
    Otherwise i can see where you’re coming from, medicine is still kind of primitive in that regard.

  • George Holland

    Three men that would have died are still alive. I think they will all say it was worth any future side effects.

  • Arturo Guadarrama

    A cousin of mine had been diagnosed in the first stage of Leukemia. I wonder if you will be able to give him your amazing treatment?… What could I do about it?… Please, contact me as soon as possible. We live in México City. Thank you.

  • Solitha


    The article itself says “that the T cells stay in circulation”. No one said anything about them magically disappearing.

    It also said it killed all B cells, healthy and cancerous, not “made to do one thing and has done that one thing and gone away”.

    “As someone who is studying the medical field i can see these issues coming up and this is my first year.”

    Ask the patients if they prefer side effects or the sure death they were facing.

    As someone with no medical studies under my belt, I would suggest you indulge in a few English and Reading Comprehension classes while you study the medical field. Please.

  • lilly

    @ anthony… you made my day.. thank you… HI EVERYBODY!!. HI DR NICK!

  • Jacob

    @ Anthony:

    No offense, but “This type of medicine will probably have side effects! We don’t even know what all the side effects will be yet!” is a horrible reason to not study a type of medicine.

    I mean, I honestly can’t think of any possible worse reason. “We don’t know what the medicine does yet, so we shouldn’t consider it or test it.”

    Um . . .

  • Cathy

    The point of this was that it was a last ditch effort to save these patient’s lives, and it worked. They would be dead otherwise. They will require closed monitoring and may have other complications, but they are ALIVE when they would have otherwise been dead. It’s not a magic bullet, but it’s definitely a promising avenue to explore for later treatments. (On that note, if you are healthy, look into becoming a platelet donor. It’s something you can do that doesn’t cost anything but two hours of your time every few weeks, and provides three critical infusions of platelets and white blood cells for immuno compromised patients such as these guys.)

  • Gorbin Wafflemunch

    Given the choice of certain death and a credible long shot (credible being the operative word here), I’ll take the long shot any day of the week and twice on Sunday. This was a gamble for all involved, yes – but it paid off. When at the end of one’s rope, what does one have to lose by trying?

    This victory comes at a price, no doubt – but as a proof of concept it’s a stunning result.

    Figuring out the optimum number of T-Cells to modify so they don’t go overboard and a way to switch them off when they’ve done their job – a killswitch for lack of a better term would’ve been nice, but considering the constraints of time and resources they were under this is a triumph no matter how you slice it.

  • Colin Bisset

    A “kill switch” for the T cells would not work. The reason the patients have few B cells is that the introduced T cells are killing them because they are cancerous. The underlying cancer, which consists of the cancerous stem cells that are producing the B cells, is still present in the patients’ bodies. This is a treatment (an amazing one), not a cure.

  • Gorbin Wafflemunch

    According to the brief above the T-Cells killed B-Cells regardless if they were cancerous or not and may continue to persist in their system for years after being introduced. Which seems like a double-edged sword – continuous, targeted cancer destruction but an inability to maintain a healthy number of B-Cells.

    Something that could stop, slow down or otherwise control these modified T-Cells would probably be helpful in using such a treatment in the future.

  • Iain

    A friend of mine had some cancer problem with his kidneys and it was stopped. Later he died from it, but as he was going down hill we asked him if he was bitter and his answer was
    “No, I got an extra ten years, how can I be bitter about that?”

  • Viv

    This is interesting from the point of view that a Dr Burzynski in Texas US has been curing cancer patients for decades with his treatment. He uses Proteins and enzyms. Look him up on the website or watch the interesting video.

    Cancer ‘Burzynski: Cancer is Serious Business’ Full-Length Documentary

  • Davey

    My father died from CML leukemia. My son survived ALL leukemia. Both were treated with conventional chemotherapy drugs. They’re horrible. My father’s bone marrow was accidentally killed by the induction chemo. My son had 3 years of puking, a bald head, and prednisone-swollen face. His mental functioning is impaired by whole-brain radiation and he is probably sterile. I’m grateful that he’s alive but I wish it hadn’t been so brutal.

    I’m stoked about this research. We need smarter, non-toxic tools.

  • lyllyth

    It’s a great step, now they have to figure out how to give these T cells ultra short telomeres, or some sort of definite kill-switch.

    The cost of the rest of your ENTIRE immune system is FAR TOO GREAT a price to pay, if you ask me. Although if the choice is dead next month or dead next year, I might pick next year, too.

    They’ve turned these trial patients into the world’s first documented non-HIV AIDS patients.
    Remember? *Acquired* Immuno-Deficiency Syndrome.

  • http://discovermagazine fabe

    to whom it may concern my sister is dying of small celled lung cancer if anyone has any info i can use to help her please please please email me at

  • angie

    I think this is great progress for anyone with a terminal diagnoses! I think my uncle would volunteer to test it on his terminal prostate cancer! He is a young 45 years old with twin boys who are only 14 yrs old. I think it is safe to say that a few side effects are nothing compared to the death sentence he currently has. He has tried some other experimental treatments which have all failed. HIs cancer is still on the spread! His Dr. here at the UW Madison hospital and clinics say his case is one of the most aggressive forms of prostate cancer they have seen. So If this treatment can help him! Bring it on! Its finally nice to see something that might help given all the money that has been put into cancer research. Even the slightest bit of progress really restores hope…. No need to be kill JOY!!!!! Lets us enjoy this very, very slim margin of hope!

  • Kap

    I think it’s a great start on what should be a long and interesting journey of discovery and investigation. Congrats to the three patients who were gifted more time. Congrats to the brilliant scientists who’ve figured out the starting points.

    And thank you to the reader who reminds people to become platelet donors — it saved my life, and it saved my son’s.

  • Rebecca Reddoch

    Cancer is very comlex disease and in fact is many diseases since it is can come from an almost infinite variety of genetic mutations. The docs will learn from this and changes will be tried and hopefully, many decades from now, we will have made some progress. Such seeming baby steps are frustrating to those with Damocles sword hanging over them.

    Concerning the ovewhelming of the body’s waste removal systems, some alternative cancer treatmens have already come up with some good supports. The coffee enema, as primitive as it sounds, is pretty good at keeping the toxins moving out of the liver as cancerous tissue is broken down by the immune system. Good hydration is always important. Keeping the skin absolutely free of lotions and chemicals even factors in. Obviously you would support the kidneys with good hydration and constantly monitor in case dialysis was warranted perhaps.

    I pulled my late husband, who had liver cancer, out of hepatic encephalopathy on 2 occasions. The first time was brought on by veno occlusive disease from over radiation, aggravated by an episode of eating meat (those proteins need a healthy liver to digest). It resolved with freshly made carrot juice 8 times per day. The second was brought on by hemorrhagic gastritis and a j tube in the small intestine that did not allow for the usual fiber intake to clean the colon. The combination of dying red blood cells and the low colon motility propelled him into grade 3 hepatic coma. The coffee enema pulled him out and gave us a few more weeks with him.

  • Rebecca Reddoch

    One more hint for the docs managing the waste overload from tumor breakdown. Low sodium diet. Push foods with more potassium. That seems to keep fluid from collecting and stagnating in the body. A lot of this is just about doing whatever you can to flush the waste from the body.

  • http://discovery carl barrett

    I was diagnozed with this disease several times. Took interferon treatments for a year. BEAT IT. WOW!!! I AM BLESSED!!

  • Rebecca Reddoch

    Congrats carl barrett. Keep up your spirit of appreciation and pass it on. You will encourage others.

  • Charles

    Can we make it a requirement that comments posted are not from kindergardners?

    Cancer needs to be treated, period.

    If you dont agree with the treatment, the invent a new one if you think you can.


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