10 ms·

First human injected with cancer-killing virus in clinical trial

327 points by sizzle 4y ago

TaupeRanger 4y ago
Looks interesting. Let us know in 3-5 years when the Phase III trials are done and there's an overall survival benefit beyond the standard of care at that time.
- SV_BubbleTime 4y ago
  3-5 years and previously completed phase three trials didn’t stop mRNA deployments. So, I have no idea if that is the new standard or not. Let’s hope it was a fluke, and that this on topic is a big deal.
  - lumost 4y ago
    mRNA vaccines benefited from the statistical power of having a widespread pandemic. Trials could simply do a double blind test and check how often the treatment subjects got covid vs. control. With thousands of study participants and a fast moving virus statistical power is reached quickly. For cancers, the disease is slow moving and there are fewer patients seeking experimental treatment. Fewer still are willing to chance that they are part of a control group. The patients who do participate are likely taking multiple other treatments, limiting the statistical power of the trial.
    - loonster 4y ago
      You cannot use 10 women to grow a fetus in 1 month. Likewise, you cannot have a good understanding of the long term risks without having s study that runs longterm.
      - arcticbull 4y ago
        Luckily we've been studying mRNA vaccines for over 50 years, which gave us a very good understanding of the long-term effects. What we really needed to test for was short-term effects + efficacy. These are easy to determine when 1% of the population is infected at the time of your clinical trial. I can't stress how much the COVID mRNA deployment wasn't a "#yolo" moment like some folks still continue to insist. It was a product of years and years of meticulous research and development. This put us at the finish line, and all we had to do was get over it. We also got the J&J vaccine out in basically the same amount of time - because like the mRNA vaccines, the adenoviral vector vaccine platform had about 50 years of research and development behind it. To use your analogy, we started with 10 ladies each 8 months pregnant, and we got them over the line in a month. That doesn't mean the pregnancy took a month - just that we had a head start.
        SV_BubbleTime 4y ago
        How many times did mRNA vaccines pass phase three trials in those 50 years? > We also got the J&J vaccine out in basically the same amount of time No skin off my back, but is that an example you want to use?
        ch4s3 4y ago
        Not to be overly pedantic, but having the idea in the 1970s didn't count for much, because no one could get mRNA into human cells until around 1987. The first attempt at a vaccine was around maybe 1993. I mean, directionally your right but saying "we've been studying mRNA vaccines for over 50 years" isn't really correct.
      - lebuffon 4y ago
        Interesting that you used that phrase on HN. Not sure if you ever heard that Fred Brooks said software development is also like this: "It takes nine months to have a baby, no matter how many women you put on the the job" The Mythical Man Month We now return to our regularly scheduled program...
        loonster 4y ago
        That is a much more eloquent way of putting it. I do wonder how old that phrase is.
      - throw__away7391 4y ago
        I am not a doctor nor a woman, but shouldn't the math on that work out to nine women? Also, I believe that even just one woman can grow a fetus in one month, no?
        makeset 4y ago
        > shouldn't the math on that work out to nine women? The average term being a round 40 weeks, a pregnancy “month” is 4 weeks by convention.
        danachow 4y ago
        > The average term being a round 40 weeks, a pregnancy “month” is 4 weeks by convention. This convention is news to me - though the confusion is not. Months are plain old calendar months in pregnancy (ie about 4.3 weeks). https://www.verywellfamily.com/how-many-months-pregnant-am-i-2760090 https://www.verywellfamily.com/how-many-months-pregnant-am-i... 40 weeks is by convention from estimated last menstrual period, which is of course about 2 weeks prior to fertilization - so the actual gestastional period is closer to 38 weeks (that is closer to 9 months than 10 months).
      - lamontcg 4y ago
        Vaccines either produce side effects in 3-6 months or they don't. There's no hidden time bomb in all the people who were vaccinated last year. The FDA doesn't require long term safety studies for vaccines, and all the coronavirus vaccines have met the requirements. Nothing has been rushed. We have a good understanding of this because the side effects are entirely dominated by autoimmune conditions, and we understand from the field of rheumatology how those arise. We don't need to study pregnant women for another 5 years to see if any more babies pop out after the first one. Pregnancy is done in 9 months. Autoimmune side effects from vaccines happen in 3-6.
        lamontcg 4y ago
        > This complex, specific and intricate process spans a number of months. Ultimately, though, in the absence of further stimulation by new copies of the spike protein, the immune response settles down, and effector cells—those directly and transiently involved in fighting the virus—decrease in frequency. Instead memory cells are established, poised to quickly ramp up production of antibodies, and even to replicate themselves, settling into their biological niches in our bodies until called upon once more if we happen to get infected. (This is what confers immunity to the coronavirus over the long run.) Antibody concentrations, some weeks after immunization, begin to reach their peak concentration in our blood, ultimately plateauing and beginning their slow decline. After this point, the risk of severe immunization-related complications doesn’t increase. Quite the opposite, in fact: it declines to virtually nothing after about three months. The six-month endpoint for these products is thus a rather conservative timeframe. Forget five or ten years: the way your immune system works does not allow for such long-term safety concerns. https://bostonreview.net/articles/the-long-term-safety-argument-over-covid-19-vaccines/ https://bostonreview.net/articles/the-long-term-safety-argum...
        XorNot 4y ago
        It is wild how heavily downvoted this is. Everything in this comment is correct (I also note none of the downvotes could be bothered to present any rebuttal to the claims).
        blindmute 4y ago
      - mbreese 4y ago
        This is a phase I study. The point here is to establish safety. The study believes this treatment could have a benefit for patients, but they aren’t sure if there are unknown risks. This is to establish that there aren’t any unknown risks. The eligible patient population has already advanced on therapy (meaning the current standard of care hasn’t worked). Getting patients to any sort of long-term response is the goal here. If there are any long term risks, that would be considered a good outcome (because the patient is still alive to have long term effects). Any further (heritable genetic) risks are mitigated as the patients specifically are excluded if they are planning on having children in the near future.
    - mcswell 4y ago
      Do you really need a control group for this kind of study? The growth of cancer has been studied for well over a century, with millions of cases; what would a hundred more (to take a random number) tell you? (BTW, this is a real question, not a sarcasm!)
      - yourMadness 4y ago
        The control group is needed to measure process properties / systematic error. It does not need to be a placebo group. Previous data at the same hospital does not help because the regular medicine does not run according to study protocols.
  - shadowgovt 4y ago
    It's not the new standard. Breast cancer is not contagious and has no chance of becoming a pandemic. The issue with a pandemic is every person infected is several more infectees in the future; geometric death effects instead of linear.
    - rory 4y ago
      At the risk of starting a flamewar... wasn't the difference actually just the pure volume of severe sickness and death? The clinical trials didn't even attempt to test viral spread, they tested prevention of symptoms. If suddenly 50% of the world population got breast cancer at once, I'm willing to bet we'd be fine rolling out new technologies faster than the typical standard, despite it being non-contagious.
      - ray__ 4y ago
        A major difference is that no two breast cancers are the same. You're probably correct in your second point due to the sheer demand, but developing a treatment for any cancer is not the same as developing a treatment for an infectious disease because there is no one-size-fits-all strategy. A situation like the one you describe with simultaneous onset of breast cancer in a large population would definitely facilitate research and help lead to a better standard of care, though.
- Kalanos 4y ago
  ok we will!
  - deleted 4y ago
    [deleted]
jvalencia 4y ago
Does anyone know how safe such a thing could be? What keeps the virus from mutating and being dangerous?
- toiletfuneral 4y ago
  there's a decent history of hijacking viruses for targeted delivery: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243974/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243974/
- TulliusCicero 4y ago
  That's probably why they tend to start these trials with people who are already in medically dire straits. If someone is currently pretty much guaranteed to die -- which is what the eligibility criteria sound like to me, someone correct me if I'm wrong here -- then there's less concern compared to accidentally killing someone who was doing fine before. And those initial trials will let you check for things like virus mutations. They did the same thing with the pig heart transplant recently, did the operation on a guy who desperately needed a new heart but was ineligible for a regular transplant.
  - throwaway290 4y ago
    I think jvalencia meant what if the virus transmits between humans for example, and escapes into the wild.
    - sizzle 4y ago
      oh crap, didn't even consider this as a possible 'side effect' I hope someone on HN who has the right scientific background can explain why this is highly unlikely or an impossible outcome..
      - throwaway290 4y ago
        I would presume because flu vaccines etc. require infecting a human with a virus in some form or another, there was plenty of time to ensure engineered viruses do not transmit.
jaqalopes 4y ago
[flagged]
- michaelmcdonald 4y ago
  I, for one, welcome our impending zombie overlords.
  - xwdv 4y ago
    Can’t be much worse than the previous overlords.
    - ffhhj 4y ago
      The good news is zombies won't burn us out with some soul-sucking methodology.
      - Apocryphon 4y ago
        The “zombies” in that story were technically vampires, so they might still provide that type of methodology.
- ALittleLight 4y ago
  Such comments aren't obligatory. Comments that are purely memes or jokes don't belong as top level comments (if at all).
fnordpiglet 4y ago
God bless and good luck to the lady who received this treatment. I hope it opens the way to a lot of people getting the same treatment, but first I hope it saves her life.
Gatsky 4y ago
These engineered viruses are remarkable feats of biotechnology. I have to wonder if they are great treatments though. The issue is complexity. The virions have to achieve contact with the target cell, penetration, avoidance of host immunity, delivery of whatever their effector function is, and hopefully then killing the cancer cell. They also need to do this for a substantial portion of the billions of cancer cells in the patient (not all cancer cells, bystander killing is part of the way they work), which display considerable heterogeneity. This is a pretty complex chain of events, which is a disadvantage when dealing with an evolvable target like cancer. Other (effective) antibody or small molecule therapies have simpler mechanisms of action. The viruses we know and love have evolved over long periods to infect small populations of homogeneous cells, quite different to the task here. I guess we will see.
- pazimzadeh 4y ago
  If there is niche for the virus in the cancer cells then the virus could in theory and adapt as well. It depends on how the virus was constructed. In addition to directly killing tumor cells, a small number of dead cells could be processed into antigens by a macrophage nearby and presented to a T-cell. If in some cases the virus can get in to the tumor cell but can't kill it, it's possible the virus can still be detected and presented on MHC Class I (unless it's suppressed) of the tumor cell by neighboring Natural Killer cells. That's why it's important to reverse the tolerogenic environment that the tumor creates around itself. The viral infection will hopefully go a long way towards waking up the immune system up.
  - Gatsky 4y ago
    Real time adapting viruses are not really something that exists, unless I'm mistaken. They would be very hard to build not least because the problem is poorly specified and would introduce an unpredictable element which is undesirable for a medical therapy. Yeah using viruses to potentiate anti-tumor immunity is an interesting idea. But returning to my main point, this is creating additional complexities. Most successful cancer therapies tend to do one thing well. Reliable synergy between treatments is actually quite rare. Peter Sorger has published some interesting stuff about this point. The reason combination therapies work better is because it is harder for a cancer cell to be resistant to everything, not because the drugs synergise to kill otherwise resistant cells. MHC Class I mediated killing is done by effector T cells, not NK cells. Cancers of course learn to turn off peptide presentation via MHC, which stops anti-PD-1 drugs from working. Interestingly many real viruses stop the cells they infect from displaying peptides to escape T cell mediated destruction. There are already studies of treatments which ramp up the immune response without killing off cancer cells much eg intratumoral STING agonists, mRNA compounds which induce manufacture of chemokines. They don't work that well, so I think the cancer killing capacity of the virus is important. Otherwise there are simpler more 'drug-like' ways to attract more effector cells to the tumor.
chromatin 4y ago
HN submission feedback: This is a poor submission. The linked page is just a bland study information page. This made it to the front page of HN despite being relatively free of actual information. What's more, the subject line is misleading or wrong. This is not in any way the first human application of antitumor viruses (oncolytic viral therapy which has been going on for a few years), just the first person on this study (presumably -- the link in fact doesn't even indicate FPFD [first patient, first dose] has happened).
- sizzle 4y ago
  OP here: Link to the original article: https://news.yahoo.com/first-human-patient-injected-revolutionary-140900099.html https://news.yahoo.com/first-human-patient-injected-revoluti... It obscured the link to the actual clinical trial. Also front page of Reddit: https://www.reddit.com/r/worldnews/comments/uvplpj/first_human_patient_injected_with_revolutionary/ https://www.reddit.com/r/worldnews/comments/uvplpj/first_hum... AMA with creator of vaccinia oncolytic viruses here: https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i9n7nbg/ https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i...
sizzle 4y ago
OP Here: Link to the original article: https://news.yahoo.com/first-human-patient-injected-revolutionary-140900099.html https://news.yahoo.com/first-human-patient-injected-revoluti... It obscured the link to the actual clinical trial. Also front page of Reddit: https://www.reddit.com/r/worldnews/comments/uvplpj/first_human_patient_injected_with_revolutionary/ https://www.reddit.com/r/worldnews/comments/uvplpj/first_hum... AMA with creator of vaccinia oncolytic viruses here: https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i9n7nbg/ https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i...
hentrep 4y ago
Disclaimer: I’ve spent my career across oncology R&D and commercial roles, but have never worked on oncolytic viruses. Title is misleading - this is a first in human, safety/dose-escalation study for this particular oncolytic virus. Oncolytic viruses have been in clinical development for quite some time. In response to the predictable “let us know when it works in humans” responses we see following sensationalist clinical research headlines, in 2015 we actually saw an oncolytic virus approved in the US: T-VEC for inoperable melanoma [0] A few interesting things here from my point of view. First, they’re engineering the virus to infect cancer cells and overexpress PD-L1 to prime for enhanced immune-mediated killing. This could help a “cold” tumor turn “hot” by remodeling the tumor microenvironment. Second, the virus will also overexpress a symporter in the cancer cells which allows for targeted imaging and monitoring of tumor activity and cell death. There’s a nice graphical abstract available for reference [1] Importantly, they’re assessing this in TNBC as it is associated with a very poor prognosis and has been validated as responsive to anti-PD-1 immunotherapies (eg, Keytruda/pembrolizumab)[2] For the curious, there’s a preclinical Nature paper from June 2021 describing this in pancreatic cancer cells [3] [0] https://en.wikipedia.org/wiki/Talimogene_laherparepvec https://en.wikipedia.org/wiki/Talimogene_laherparepvec [1] https://pubmed.ncbi.nlm.nih.gov/35118191/ https://pubmed.ncbi.nlm.nih.gov/35118191/ [2] https://www.nejm.org/doi/full/10.1056/NEJMoa1910549 https://www.nejm.org/doi/full/10.1056/NEJMoa1910549 [3] https://www.nature.com/articles/s41417-021-00350-4 https://www.nature.com/articles/s41417-021-00350-4
- sizzle 4y ago
  Here is the original article with similar title: https://news.yahoo.com/first-human-patient-injected-revolutionary-140900099.html https://news.yahoo.com/first-human-patient-injected-revoluti... It obscured the link to the actual clinical trial. Also front page of Reddit: https://www.reddit.com/r/worldnews/comments/uvplpj/first_human_patient_injected_with_revolutionary/ https://www.reddit.com/r/worldnews/comments/uvplpj/first_hum... AMA with creator of vaccinia oncolytic viruses here: https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i9n7nbg/ https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i... Thank you for the work you do.
  - ddingus 4y ago
deleted 4y ago
[deleted]
hda2 4y ago
What stops this virus from evolving/mutating to kill healthy cells and then becoming contagious? Do we have effective measures to stop this virus in the event that this occurs? If so, what are they? Edit: I don't know a lot about virology. Please don't downvote an honest question.
- jart 4y ago
  According to Google the virus population on planet earth is 10,000,000,000,000,000,000,000,000,000,000 so there's a lot of mutation going on and we're still here. So random mutation of one more well-intentioned virus that kills cancer probably isn't a threat.
  - pjerem 4y ago
    And even, to become a threat, the virus may need to mutate several times just to become even a little contagious. Most viruses are not really contagious (as in respiratory contagious viruses).
  - optimalsolver 4y ago
    How many of those are specially adapted to interact with human cells?
    - zaarn 4y ago
      COVID-19 comes to mind as well as literally any human virus infection.
      - optimalsolver 4y ago
        Ok, so a couple of dozen out of whatever number OP posted?
        zaarn 4y ago
        That's a population number. COVID alone accounts for 10^11 virus particles in a single human during peak infection, or about 10^19 in total. That is getting close to the 10^31 total. But to be precise about all viruses; A over-the-thumb estimate is 10^24 viruses of the total population of the earth's biosphere are actively living in the collective biomass of the human species at every moment. That is merely the population of viruses currently alive in all humans, ranging from the ones going hunt on bacteria in our gut to the ones living in our blood and flesh. If we estimate the weight of a virion particle to be 1 femtogram (which is roughly the dry mass of a covid particle), that yields you 10^6 kilograms of biomatter. About the weight of a Saturn V rocket. So not a couple dozen out of the number OP posted. It's a significiant number. And you have to keep in mind that OP's number does not only include the human virion particles but all virion particles in nature, including megaviruses, virions, virophages, bacteriophages etc. Most of those are not compatible with how human bodies work, probably 99.999% of viruses in nature will not survive in a human body, they're specialised to hunt other things. By introducing a few nanograms of virus material to a human, you're contributing effectively 0% to the natural virus levels in just a single human, in the grand view of things it does not matter. And the moment these viruses escape, they're subject to evolutionary pressure, meaning they will evolve to not kill their hosts very quickly or perish before they get a chance.
WalterBright 4y ago
"60 Minutes" ran a piece a couple years ago about a modified polio virus injected into people with inoperable brain tumors. A couple patients were cured, one died as I recall. Haven't heard about it since.
Hackbraten 4y ago
On Firefox, this page shows me just skeleton placeholders where the text is supposed to be, and nothing ever loads. Even with content blockers disabled.
- viktorcode 4y ago
  Same on Safari.
- Ajef 4y ago
  Same on my desktop with Chrome, Firefox and Edge as well as on my Android device (Firefox, DuckDuckGo-Browser). I can see the text shortly while the page is still loading.

327 points by sizzle 4y ago

Looks interesting. Let us know in 3-5 years when the Phase III trials are done and there's an overall survival benefit beyond the standard of care at that time.

SV_BubbleTime 4y ago
3-5 years and previously completed phase three trials didn’t stop mRNA deployments. So, I have no idea if that is the new standard or not. Let’s hope it was a fluke, and that this on topic is a big deal.
- lumost 4y ago
  mRNA vaccines benefited from the statistical power of having a widespread pandemic. Trials could simply do a double blind test and check how often the treatment subjects got covid vs. control. With thousands of study participants and a fast moving virus statistical power is reached quickly. For cancers, the disease is slow moving and there are fewer patients seeking experimental treatment. Fewer still are willing to chance that they are part of a control group. The patients who do participate are likely taking multiple other treatments, limiting the statistical power of the trial.
  - loonster 4y ago
    You cannot use 10 women to grow a fetus in 1 month. Likewise, you cannot have a good understanding of the long term risks without having s study that runs longterm.
    - arcticbull 4y ago
      Luckily we've been studying mRNA vaccines for over 50 years, which gave us a very good understanding of the long-term effects. What we really needed to test for was short-term effects + efficacy. These are easy to determine when 1% of the population is infected at the time of your clinical trial. I can't stress how much the COVID mRNA deployment wasn't a "#yolo" moment like some folks still continue to insist. It was a product of years and years of meticulous research and development. This put us at the finish line, and all we had to do was get over it. We also got the J&J vaccine out in basically the same amount of time - because like the mRNA vaccines, the adenoviral vector vaccine platform had about 50 years of research and development behind it. To use your analogy, we started with 10 ladies each 8 months pregnant, and we got them over the line in a month. That doesn't mean the pregnancy took a month - just that we had a head start.
      - SV_BubbleTime 4y ago
        How many times did mRNA vaccines pass phase three trials in those 50 years? > We also got the J&J vaccine out in basically the same amount of time No skin off my back, but is that an example you want to use?
      - ch4s3 4y ago
        Not to be overly pedantic, but having the idea in the 1970s didn't count for much, because no one could get mRNA into human cells until around 1987. The first attempt at a vaccine was around maybe 1993. I mean, directionally your right but saying "we've been studying mRNA vaccines for over 50 years" isn't really correct.
    - lebuffon 4y ago
      Interesting that you used that phrase on HN. Not sure if you ever heard that Fred Brooks said software development is also like this: "It takes nine months to have a baby, no matter how many women you put on the the job" The Mythical Man Month We now return to our regularly scheduled program...
      - loonster 4y ago
        That is a much more eloquent way of putting it. I do wonder how old that phrase is.
    - throw__away7391 4y ago
      I am not a doctor nor a woman, but shouldn't the math on that work out to nine women? Also, I believe that even just one woman can grow a fetus in one month, no?
      - makeset 4y ago
        > shouldn't the math on that work out to nine women? The average term being a round 40 weeks, a pregnancy “month” is 4 weeks by convention.
        danachow 4y ago
        > The average term being a round 40 weeks, a pregnancy “month” is 4 weeks by convention. This convention is news to me - though the confusion is not. Months are plain old calendar months in pregnancy (ie about 4.3 weeks). https://www.verywellfamily.com/how-many-months-pregnant-am-i-2760090 https://www.verywellfamily.com/how-many-months-pregnant-am-i... 40 weeks is by convention from estimated last menstrual period, which is of course about 2 weeks prior to fertilization - so the actual gestastional period is closer to 38 weeks (that is closer to 9 months than 10 months).
    - lamontcg 4y ago
      Vaccines either produce side effects in 3-6 months or they don't. There's no hidden time bomb in all the people who were vaccinated last year. The FDA doesn't require long term safety studies for vaccines, and all the coronavirus vaccines have met the requirements. Nothing has been rushed. We have a good understanding of this because the side effects are entirely dominated by autoimmune conditions, and we understand from the field of rheumatology how those arise. We don't need to study pregnant women for another 5 years to see if any more babies pop out after the first one. Pregnancy is done in 9 months. Autoimmune side effects from vaccines happen in 3-6.
      - lamontcg 4y ago
        > This complex, specific and intricate process spans a number of months. Ultimately, though, in the absence of further stimulation by new copies of the spike protein, the immune response settles down, and effector cells—those directly and transiently involved in fighting the virus—decrease in frequency. Instead memory cells are established, poised to quickly ramp up production of antibodies, and even to replicate themselves, settling into their biological niches in our bodies until called upon once more if we happen to get infected. (This is what confers immunity to the coronavirus over the long run.) Antibody concentrations, some weeks after immunization, begin to reach their peak concentration in our blood, ultimately plateauing and beginning their slow decline. After this point, the risk of severe immunization-related complications doesn’t increase. Quite the opposite, in fact: it declines to virtually nothing after about three months. The six-month endpoint for these products is thus a rather conservative timeframe. Forget five or ten years: the way your immune system works does not allow for such long-term safety concerns. https://bostonreview.net/articles/the-long-term-safety-argument-over-covid-19-vaccines/ https://bostonreview.net/articles/the-long-term-safety-argum...
      - XorNot 4y ago
        It is wild how heavily downvoted this is. Everything in this comment is correct (I also note none of the downvotes could be bothered to present any rebuttal to the claims).
        blindmute 4y ago
    - mbreese 4y ago
      This is a phase I study. The point here is to establish safety. The study believes this treatment could have a benefit for patients, but they aren’t sure if there are unknown risks. This is to establish that there aren’t any unknown risks. The eligible patient population has already advanced on therapy (meaning the current standard of care hasn’t worked). Getting patients to any sort of long-term response is the goal here. If there are any long term risks, that would be considered a good outcome (because the patient is still alive to have long term effects). Any further (heritable genetic) risks are mitigated as the patients specifically are excluded if they are planning on having children in the near future.
  - mcswell 4y ago
    Do you really need a control group for this kind of study? The growth of cancer has been studied for well over a century, with millions of cases; what would a hundred more (to take a random number) tell you? (BTW, this is a real question, not a sarcasm!)
    - yourMadness 4y ago
      The control group is needed to measure process properties / systematic error. It does not need to be a placebo group. Previous data at the same hospital does not help because the regular medicine does not run according to study protocols.
- shadowgovt 4y ago
  It's not the new standard. Breast cancer is not contagious and has no chance of becoming a pandemic. The issue with a pandemic is every person infected is several more infectees in the future; geometric death effects instead of linear.
  - rory 4y ago
    At the risk of starting a flamewar... wasn't the difference actually just the pure volume of severe sickness and death? The clinical trials didn't even attempt to test viral spread, they tested prevention of symptoms. If suddenly 50% of the world population got breast cancer at once, I'm willing to bet we'd be fine rolling out new technologies faster than the typical standard, despite it being non-contagious.
    - ray__ 4y ago
      A major difference is that no two breast cancers are the same. You're probably correct in your second point due to the sheer demand, but developing a treatment for any cancer is not the same as developing a treatment for an infectious disease because there is no one-size-fits-all strategy. A situation like the one you describe with simultaneous onset of breast cancer in a large population would definitely facilitate research and help lead to a better standard of care, though.
Kalanos 4y ago
ok we will!
- deleted 4y ago
  [deleted]

jvalencia 4y ago

Does anyone know how safe such a thing could be? What keeps the virus from mutating and being dangerous?

toiletfuneral 4y ago
there's a decent history of hijacking viruses for targeted delivery: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243974/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243974/
TulliusCicero 4y ago
That's probably why they tend to start these trials with people who are already in medically dire straits. If someone is currently pretty much guaranteed to die -- which is what the eligibility criteria sound like to me, someone correct me if I'm wrong here -- then there's less concern compared to accidentally killing someone who was doing fine before. And those initial trials will let you check for things like virus mutations. They did the same thing with the pig heart transplant recently, did the operation on a guy who desperately needed a new heart but was ineligible for a regular transplant.
- throwaway290 4y ago
  I think jvalencia meant what if the virus transmits between humans for example, and escapes into the wild.
  - sizzle 4y ago
    oh crap, didn't even consider this as a possible 'side effect' I hope someone on HN who has the right scientific background can explain why this is highly unlikely or an impossible outcome..
    - throwaway290 4y ago
      I would presume because flu vaccines etc. require infecting a human with a virus in some form or another, there was plenty of time to ensure engineered viruses do not transmit.

jaqalopes 4y ago

[flagged]

michaelmcdonald 4y ago
I, for one, welcome our impending zombie overlords.
- xwdv 4y ago
  Can’t be much worse than the previous overlords.
  - ffhhj 4y ago
    The good news is zombies won't burn us out with some soul-sucking methodology.
    - Apocryphon 4y ago
      The “zombies” in that story were technically vampires, so they might still provide that type of methodology.
ALittleLight 4y ago
Such comments aren't obligatory. Comments that are purely memes or jokes don't belong as top level comments (if at all).

fnordpiglet 4y ago

God bless and good luck to the lady who received this treatment. I hope it opens the way to a lot of people getting the same treatment, but first I hope it saves her life.

Gatsky 4y ago

These engineered viruses are remarkable feats of biotechnology. I have to wonder if they are great treatments though. The issue is complexity. The virions have to achieve contact with the target cell, penetration, avoidance of host immunity, delivery of whatever their effector function is, and hopefully then killing the cancer cell. They also need to do this for a substantial portion of the billions of cancer cells in the patient (not all cancer cells, bystander killing is part of the way they work), which display considerable heterogeneity. This is a pretty complex chain of events, which is a disadvantage when dealing with an evolvable target like cancer. Other (effective) antibody or small molecule therapies have simpler mechanisms of action. The viruses we know and love have evolved over long periods to infect small populations of homogeneous cells, quite different to the task here. I guess we will see.

pazimzadeh 4y ago
If there is niche for the virus in the cancer cells then the virus could in theory and adapt as well. It depends on how the virus was constructed. In addition to directly killing tumor cells, a small number of dead cells could be processed into antigens by a macrophage nearby and presented to a T-cell. If in some cases the virus can get in to the tumor cell but can't kill it, it's possible the virus can still be detected and presented on MHC Class I (unless it's suppressed) of the tumor cell by neighboring Natural Killer cells. That's why it's important to reverse the tolerogenic environment that the tumor creates around itself. The viral infection will hopefully go a long way towards waking up the immune system up.
- Gatsky 4y ago
  Real time adapting viruses are not really something that exists, unless I'm mistaken. They would be very hard to build not least because the problem is poorly specified and would introduce an unpredictable element which is undesirable for a medical therapy. Yeah using viruses to potentiate anti-tumor immunity is an interesting idea. But returning to my main point, this is creating additional complexities. Most successful cancer therapies tend to do one thing well. Reliable synergy between treatments is actually quite rare. Peter Sorger has published some interesting stuff about this point. The reason combination therapies work better is because it is harder for a cancer cell to be resistant to everything, not because the drugs synergise to kill otherwise resistant cells. MHC Class I mediated killing is done by effector T cells, not NK cells. Cancers of course learn to turn off peptide presentation via MHC, which stops anti-PD-1 drugs from working. Interestingly many real viruses stop the cells they infect from displaying peptides to escape T cell mediated destruction. There are already studies of treatments which ramp up the immune response without killing off cancer cells much eg intratumoral STING agonists, mRNA compounds which induce manufacture of chemokines. They don't work that well, so I think the cancer killing capacity of the virus is important. Otherwise there are simpler more 'drug-like' ways to attract more effector cells to the tumor.

chromatin 4y ago

HN submission feedback: This is a poor submission. The linked page is just a bland study information page. This made it to the front page of HN despite being relatively free of actual information. What's more, the subject line is misleading or wrong. This is not in any way the first human application of antitumor viruses (oncolytic viral therapy which has been going on for a few years), just the first person on this study (presumably -- the link in fact doesn't even indicate FPFD [first patient, first dose] has happened).

sizzle 4y ago
OP here: Link to the original article: https://news.yahoo.com/first-human-patient-injected-revolutionary-140900099.html https://news.yahoo.com/first-human-patient-injected-revoluti... It obscured the link to the actual clinical trial. Also front page of Reddit: https://www.reddit.com/r/worldnews/comments/uvplpj/first_human_patient_injected_with_revolutionary/ https://www.reddit.com/r/worldnews/comments/uvplpj/first_hum... AMA with creator of vaccinia oncolytic viruses here: https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i9n7nbg/ https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i...

sizzle 4y ago

OP Here: Link to the original article: https://news.yahoo.com/first-human-patient-injected-revolutionary-140900099.html https://news.yahoo.com/first-human-patient-injected-revoluti... It obscured the link to the actual clinical trial. Also front page of Reddit: https://www.reddit.com/r/worldnews/comments/uvplpj/first_human_patient_injected_with_revolutionary/ https://www.reddit.com/r/worldnews/comments/uvplpj/first_hum... AMA with creator of vaccinia oncolytic viruses here: https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i9n7nbg/ https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i...

hentrep 4y ago

Disclaimer: I’ve spent my career across oncology R&D and commercial roles, but have never worked on oncolytic viruses. Title is misleading - this is a first in human, safety/dose-escalation study for this particular oncolytic virus. Oncolytic viruses have been in clinical development for quite some time. In response to the predictable “let us know when it works in humans” responses we see following sensationalist clinical research headlines, in 2015 we actually saw an oncolytic virus approved in the US: T-VEC for inoperable melanoma [0] A few interesting things here from my point of view. First, they’re engineering the virus to infect cancer cells and overexpress PD-L1 to prime for enhanced immune-mediated killing. This could help a “cold” tumor turn “hot” by remodeling the tumor microenvironment. Second, the virus will also overexpress a symporter in the cancer cells which allows for targeted imaging and monitoring of tumor activity and cell death. There’s a nice graphical abstract available for reference [1] Importantly, they’re assessing this in TNBC as it is associated with a very poor prognosis and has been validated as responsive to anti-PD-1 immunotherapies (eg, Keytruda/pembrolizumab)[2] For the curious, there’s a preclinical Nature paper from June 2021 describing this in pancreatic cancer cells [3] [0] https://en.wikipedia.org/wiki/Talimogene_laherparepvec https://en.wikipedia.org/wiki/Talimogene_laherparepvec [1] https://pubmed.ncbi.nlm.nih.gov/35118191/ https://pubmed.ncbi.nlm.nih.gov/35118191/ [2] https://www.nejm.org/doi/full/10.1056/NEJMoa1910549 https://www.nejm.org/doi/full/10.1056/NEJMoa1910549 [3] https://www.nature.com/articles/s41417-021-00350-4 https://www.nature.com/articles/s41417-021-00350-4

sizzle 4y ago
Here is the original article with similar title: https://news.yahoo.com/first-human-patient-injected-revolutionary-140900099.html https://news.yahoo.com/first-human-patient-injected-revoluti... It obscured the link to the actual clinical trial. Also front page of Reddit: https://www.reddit.com/r/worldnews/comments/uvplpj/first_human_patient_injected_with_revolutionary/ https://www.reddit.com/r/worldnews/comments/uvplpj/first_hum... AMA with creator of vaccinia oncolytic viruses here: https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i9n7nbg/ https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i... Thank you for the work you do.
- ddingus 4y ago

deleted 4y ago

[deleted]

hda2 4y ago

What stops this virus from evolving/mutating to kill healthy cells and then becoming contagious? Do we have effective measures to stop this virus in the event that this occurs? If so, what are they? Edit: I don't know a lot about virology. Please don't downvote an honest question.

jart 4y ago
According to Google the virus population on planet earth is 10,000,000,000,000,000,000,000,000,000,000 so there's a lot of mutation going on and we're still here. So random mutation of one more well-intentioned virus that kills cancer probably isn't a threat.
- pjerem 4y ago
  And even, to become a threat, the virus may need to mutate several times just to become even a little contagious. Most viruses are not really contagious (as in respiratory contagious viruses).
- optimalsolver 4y ago
  How many of those are specially adapted to interact with human cells?
  - zaarn 4y ago
    COVID-19 comes to mind as well as literally any human virus infection.
    - optimalsolver 4y ago
      Ok, so a couple of dozen out of whatever number OP posted?
      - zaarn 4y ago
        That's a population number. COVID alone accounts for 10^11 virus particles in a single human during peak infection, or about 10^19 in total. That is getting close to the 10^31 total. But to be precise about all viruses; A over-the-thumb estimate is 10^24 viruses of the total population of the earth's biosphere are actively living in the collective biomass of the human species at every moment. That is merely the population of viruses currently alive in all humans, ranging from the ones going hunt on bacteria in our gut to the ones living in our blood and flesh. If we estimate the weight of a virion particle to be 1 femtogram (which is roughly the dry mass of a covid particle), that yields you 10^6 kilograms of biomatter. About the weight of a Saturn V rocket. So not a couple dozen out of the number OP posted. It's a significiant number. And you have to keep in mind that OP's number does not only include the human virion particles but all virion particles in nature, including megaviruses, virions, virophages, bacteriophages etc. Most of those are not compatible with how human bodies work, probably 99.999% of viruses in nature will not survive in a human body, they're specialised to hunt other things. By introducing a few nanograms of virus material to a human, you're contributing effectively 0% to the natural virus levels in just a single human, in the grand view of things it does not matter. And the moment these viruses escape, they're subject to evolutionary pressure, meaning they will evolve to not kill their hosts very quickly or perish before they get a chance.

WalterBright 4y ago

"60 Minutes" ran a piece a couple years ago about a modified polio virus injected into people with inoperable brain tumors. A couple patients were cured, one died as I recall. Haven't heard about it since.

Hackbraten 4y ago

On Firefox, this page shows me just skeleton placeholders where the text is supposed to be, and nothing ever loads. Even with content blockers disabled.

viktorcode 4y ago
Same on Safari.
Ajef 4y ago
Same on my desktop with Chrome, Firefox and Edge as well as on my Android device (Firefox, DuckDuckGo-Browser). I can see the text shortly while the page is still loading.