6 ms·

Cancer therapy by RNA delivery to dendritic cells

• teekert 10y ago
  This link does work, assuming it is the same article: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature18300.html http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...
  • VSerge 10y ago
    thanks
• superfx 10y ago
  Here's the full article for those interested: http://rdcu.be/iFZr http://rdcu.be/iFZr
  • baldfat 10y ago
    Thank you for the link
• brudgers 10y ago
  The breaking story in the popular press: http://www.independent.co.uk/news/science/cancer-vaccine-immunotherapy-universal-immune-system-rna-nature-journal-a7060181.html http://www.independent.co.uk/news/science/cancer-vaccine-imm...
• baldfat 10y ago
  Paywall: I read this as an ability to help in immunotherapy which works like a vaccine. I really am interested in what types of cancer this works with the strongest effect. They list soft tumors in Lungs. The bellow citation seems to show that these are something that could work on all cancer types and is cheap. These are exciting times. Now it will be another 5 years till we see this even in a trial for children? (Son and sister died of cancer and my daughter's 10 year old friend (same cancer as my sister) is in immunotherapy trial which we are praying for a miracle for her reoccurring brain cancer. > RNA-LPX vaccines are fast and inexpensive to produce, and virtually any tumour antigen can be encoded by RNA.
  • Aelinsaar 10y ago
    It's very exciting, but as these therapies become more successful, we're going to have to tackle the adverse reactions both acute, and chronic. Granted, you're surviving cancer so that's not the primary concern, but it will be a concern.
    • baldfat 10y ago
      Well that is the Number One Reason why they are going immuntheraphy the side effects are minor compared to Chemo and Radiation. This is your own body fighting the cancer.
      • Aelinsaar 10y ago
        I don't think "Minor" is accurate. A good friend just went through this to beat a strange form of metastatic blood cancer, and he was in the ICU for a week as a direct result. (and essentially comatose) It was worth it, since he went from, "Plan your death" to, "Full remission!". Still, he was strong going in, a lot of people would have died. Right now, there's still a lot of art to the balance between having your immune system fight hard enough to kill the cancer, without setting off a cytokine storm that kills you. There's also the issue of longer term autoimmune complications, which I suspect will turn out to be the "secondary cancers" of the immunotherapy world.
      • rcthompson 10y ago
        There's nothing to say that leveraging your own immune system will necessarily reduce the frequency or severity of side effects relative to current therapies. Your immune system is quite capable of killing just about any cell in your body, foreign or not. The multitude of different autoimmune diseases are clear evidence of that fact.
  • Deusdies 10y ago
    Out of curiosity, what brain cancer does she have? I had a Grade II astrocytoma in 2013, came back in Sept 2015 as Grade III. Currently undergoing chemo and feeling fine (25 years old).
• reasonattlm 10y ago
  Paper: http://dx.doi.org/10.1038/nature18300 http://dx.doi.org/10.1038/nature18300 Company release: http://biontech.de/2016/06/01/nature-publication-describes-first-example-of-a-clinically-applicable-and-systemic-mrna-cancer-immunotherapy-vaccine/ http://biontech.de/2016/06/01/nature-publication-describes-f... Really it is pretty random as to what cancer research and development gets more or less attention from the media and public. Merit has little to do with it. You should assume that any given article like this is representative of many similar ones that passed by without comment. The most important thing for any approach aspiring to be widespread in the next generation of cancer research is how costly it is to adapt the platform to any specific cancer. The only way to make real inroads in control of cancer is to crush down the cost of addressing different cancers, making it a small project rather than a whole new research initiative each time around.
  • hanklazard 10y ago
    >The only way to make real inroads in control of cancer is to crush down the cost of addressing different cancers, making it a small project rather than a whole new research initiative each time around. Agreed. And while this study's methods wouldn't be cheap per se, RNA-based methods combined with whole genome sequencing of tumors are much more cost (and time) efficient methods than approaches that require antibodies or chimeric proteins. I believe that these methods, in combination with immunotherapy, are the best candidates for future cancer therapy.
  • iskander 10y ago
    >Merit has little to do with it. Not sure if that's intentional, but the BioNTech series of trials for melanoma been called MERIT (this particular incarnation is Lipo-MERIT).
  • iskander 10y ago
    >Merit has little to do with it. Not sure if that's intentional, but the BioNTech series of trials for melanoma been called MERIT (this particular incarnation is Lipo-MERIT).
• pessimist 10y ago
  To keep things in perspective, in oncology the current success rate of treatments that enter trials is just 5%! See http://blogs.sciencemag.org/pipeline/archives/2016/06/02/are-things-getting-any-better-in-the-clinic http://blogs.sciencemag.org/pipeline/archives/2016/06/02/are.... Immunotherapy is indeed the most promising approach to cancer therapy so I'm optimistic, but the odds of success here are 1-in-20 if this is an average study, or perhaps 1-in-5 at best.
  • danieltillett 10y ago
    You certainly have chosen the right user name, but it is a logical error to use the success rate of all cancer trials to calculate the chance of success of this immunotherapy trial.
• wyldfire 10y ago
  Stupid/insensitive question: what if cancer were a species "feature" earned through evolution that helps reap people who made it through their reproductive years without accident or disease but are now more hindrance than help to the species?
  • mgraczyk 10y ago
    Most animals can get cancer, even invertebrates. Not to say your hypothesis isn't close to reasonable, but you'd have to strike the "species" part.
  • gww 10y ago
    I would argue that cancer is more of a consequence of aging, genetics, and environmental factors and not a "feature". Cells have evolved multiple mechanisms to prevent rampant and uncontrolled growth. With cancer these mechanisms are perturbed through genetic alterations due to "bad luck" or the consequences I mentioned previously.
    • RosenJD4 10y ago
      You can also think of cancer as a consequence of multicellularity. Multicellular organisms need checks on how often and by how much a group of their cells can multiply. A liver must contain a specific amount of liver cells, and cancer occurs when these cells are able to continually divide and eventually activate non liver specific genes. The cells of a multicellular organism become highly altruistic because each cell of the organism gives up its ability to reproduce in order to provide a chance for the organism's gametes to produce a new living organism. So wyldfire's original comment on Cancer being a 'feature' is not necessarily incorrect, however the explanation is. Cancer occurs when the contract that states that the Liver cells, who cannot reproduce, become able to continually divide without checks and balances. You can also almost think of Cancer as Cellular natural selection and evolution within the body. Cancer is a feature and consequence of multicellularity and likely not adaptive in any way such as sickle cell anemia and malaria resistance. An awesome book which touches on this in addition to other history or cancer is The Emperor of all Maladies http://www.amazon.com/Emperor-All-Maladies-Biography-Cancer/dp/1439170916/188-8725093-6146822?ie=UTF8&*Version*=1&*entries*=0 http://www.amazon.com/Emperor-All-Maladies-Biography-Cancer/...
• rcthompson 10y ago
  This is certainly an interesting and theoretically promising method, that, if it works, should make it fairly easy to develop specific personalized "vaccines" for each person's cancer. For background, dendritic cells are a type of antigen-presenting cells, which means their job is to pick up proteins, break them up into small pieces (antigens), and then show those pieces to T-cells, whereupon the T-cells can either say "looks like a self antigen, everything's fine" or say "that looks like a foreign antigen, raise the alarm!" and then initiate a specific immune response against that antigen. The basic concept here is that if you have a specific protein that you want to raise an immune response against, you can do so by tricking dendritic cells into producing copies of that protein, which will then get presented along with all the other antigens for inspection by T-cells. You can pull off this trick by feeding RNA that encodes the target protein to the dendritic cells, and as a bonus, the fact that there's free RNA floating around triggers anti-viral defenses, which causes the T-cells to be extra suspicious of the antigens they're inspecting (i.e. it lowers their threshold for raising an immune response). But injecting RNA directly into your spleen isn't exactly practical, so instead they found that attaching the negatively charged RNA to some positively charged lipids in a specific ratio (which results in a specific ratio of charge to mass) causes them to localize to the spleen and then get taken up, translated, and presented by dendritic cells when injected intravenously. So, put it all together, and the workflow for treating cancer looks something like this: 1. Find a protein produced by the cancer cells that is either sufficiently different from the same protein in normal cells (due to mutation) or not produced in normal cells. 2. Construct an RNA transcript that will produce that protein when translated. 3. Attach that RNA transcript to the liposomes in the appropriate ratio, and inject it into your bloodstream. 4. Let the immune system do its thing. 5. Repeat as necessary to keep the immune response active until it's killed all the cancer. Obviously step 1 is still the hard part, and the paper chose as a proof of concept two example cancers for which this step was already done. But finding a viable cancer-specific antigen is certainly orders of magnitude easier than determining the mechanism of a cancer and then developing a treatment specific to that mechanism.
  • pvnick 10y ago
    Great summary, thanks for that. This therapy appears fairly elegant. Let's hope it makes it through trials.