7 ms·

Cancer 'vaccine' that remembers and fights disease is developed by scientists

130 points by tempestn 11y ago

mchahn 11y ago
Why are all the gene-based cancer breakthroughs I've seen in the news for blood diseases? Is it easier to manipulate genes in blood?
- teekert 11y ago
  I think it is because in blood drugs and gene based treatments are the only option, surgery is simply not an option. This has always spurred the blood cancer field to take greater risks, the all or nothing approach.
  - erkkie 11y ago
    Surgery is an option, namely bone-marrow transplants. The reason blood cancers are first with these techniques boils down to having better known antigen targets to target compared to solid tumors where known antigens have more cross reactivity to other tissues (so less specificity, more side-effects).
    - carbocation 11y ago
      Despite the word "transplant", bone marrow transplants are not done surgically; they are done by infusion of donor cells into the bloodstream. Then, the cells seek out their own niche and engraft.
      - erkkie 11y ago
        Good point, you're right, not surgery, more like an (significantly invasive) procedure. Still good to differentiate from "giving a drug".
  - pacap 11y ago
    From what I remember, these blood cancer have an antigen, CD13 or something, which is unique to them - no other body part has it, making it easy to target them. Otherwise, you get the side effect of destroying your own body, the case of a woman a few years ago, who died having her lungs destroyed by immunotherapy. Lungs had the same antigen. This morning I read something hopeful in this direction - UCSF researchers designed an AND gate, so now they could trigger a T cell attack only when 2 specific antigens are present, making it much more reliable. And I could imagine these can be chained, further narrowing it down. It needs genetic sequencing to isolate. https://www.ucsf.edu/news/2016/01/401471/tricked-out-immune-cells-could-attack-cancer-spare-healthy-cells https://www.ucsf.edu/news/2016/01/401471/tricked-out-immune-... At the moment this is a terrible manual and time consuming process, so it is expensive.
    - erkkie 11y ago
      This is also why a combination of engineered T-cells and immune checkpoint inhibitors is a really winning combo. http://www.theguardian.com/society/2015/jun/01/paradigm-shift-hailed-in-treatment-of-lung-cancer http://www.theguardian.com/society/2015/jun/01/paradigm-shif...
      - AstralStorm 11y ago
        Immune checkpoint (fancy name that, you probably mean anti-autoimmune system) inhibitors main problem is the very high risk of autoimmune disorders that are hard or impossible to treat. Just toggling the suppressor will not kill clonal cells already in circulation, and those can last a long, long time, or even a lifetime. If you're unlucky, you will also get "broken" immune memory cells - which also last for life. Trading cancer for SLE or rheumatoidal arthritis etc.
- forgotpwagain 11y ago
  In general, blood cancers are more accessible than solid tumors. With blood cancers, the majority of the cancer cells are in the blood or in very well perfused tissues (bone marrow, spleen, thymus, etc), meaning that drugs/treatments can get to the targets very easily. With solid tumors, you have to deal with the complexities of the tumor microenvironment. The tumor microenvironment is the complex environment of the cancer tumor tissue. Of particular note, decreased lymphatic drainage, increased connective tissue, and aberrant angiogenesis (growth of new blood vessels) create very high interstitial fluid pressures within the tumor, limiting the ability of drugs or cells to penetrate within the tumor and "work their magic" by reaching the cells/target molecules of interest, etc. Blood cancers are a good proof-of-principle for many cancer therapies; translation to solid tumors is difficult (see challenges with CAR-T cell immunotherapy). As for gene manipulation in blood--yes, it is relatively easy to manipulate genes in blood. Hematopoetic Stem Cells (which differentiate into all different kinds of blood cells) can be withdrawn without too much difficulty, manipulated in the lab, and then reinjected into the patient.
  - agumonkey 11y ago
    Pardon the naive question, I don't know how localized therapies are today, but hasn't there been research into developing fake foreign capillaries to be implanted non invasively to deliver drugs right on target ? ps: I remember seeing more 'barbaric' version of the idea, namely metal pipes planted in the patient as a direct path. I was wondering about something more organic.
    - forgotpwagain 11y ago
      I'm not an expert, but I think there's been a variety of attempts for vascular renormalization--to restore the normal flow of vessels to allow for drug delivery, etc. Rakesh Jain's lab (at MGH) is a big player in this field and is worth looking up if you're interested. I'm not personally familiar with work in developing capillary devices, but it wouldn't surprise me at all if this was an approach under development--it certainly makes a lot of sense.
      - 11y ago
teekert 11y ago
I really appreciate the down-to-earth-ness of this interview, this man is being very honest. It's good not to create false hope and present cancer immunotherapy (yet perhaps) as the thing that will cure any cancer. However, it is the only real curative treatment next to surgery and really the only treatment that can cure metastatic cancer. At the moment though, only in small percentage of people with specific cancers (mostly melanoma, skin cancers.) So there certainly is reason to be excited, the cancer field is all over this at the moment so advances in the near future can be expected.
- dang 11y ago
  > the down-to-earth-ness of this interview That would be the interview at http://www.bbc.com/news/health-35585571 http://www.bbc.com/news/health-35585571. We changed the URL to a text version of the story.
- forgotpwagain 11y ago
  The method by which vaccinations work is immunological. I think the most exciting frontier in cancer biology is prophylactic (preventative) vaccination. If we are able to develop effective vaccines against cancers, that will very much change the game. This is currently a research frontiers area--but in 10-20 years, I believe that we will have made significant inroads on it.
  - teekert 11y ago
    Since every cancer is different in the markers it displays, I think that is unlikely to happen. It would mean an insane amount of vaccinations and the assumption that they have none to acceptable side effects.
    - mbreese 11y ago
      Not to mention the risk for an auto-immune complication... because the cancer is just slightly different from "self", any immune response will have a very high risk for auto-immune recognition. That's why CAR-T treatments are considered only in the cases where all other options have been exhausted.
deleted 11y ago
[deleted]
nonbel 11y ago
"The findings are yet to be published and reviewed." Are people really ok with this practice of researchers talking about their discoveries without having shared the methods and data (I don't care so much about the review aspect)? I'm certainly not, but apparently many think this is acceptable for some reason because I don't see any pushback.
- tominous 11y ago
  I'm biased. My wife was diagnosed with metastatic cancer 6 months ago. With current standard treatments there is a 3-year survival rate of practically zero, so to me the most important thing is getting new effective treatments developed and brought into clinical practice as soon as possible. I haven't seen the presentation about the study (a related news briefing is here [1]) so I don't know whether you're correct to say that the researchers haven't shared their methods and data. They seem quite happy to share technical details at the news briefing. However, regardless of that, I still think it is a good thing if researchers talk about their findings at an early stage, especially if the findings are as dramatic and positive as these. If a treatment is available and you have patients out there dying with no other options, then it is just wrong to hide that away. In my opinion we treat these things far too cautiously. It is not optimal for the individual and it is not optimal for society. By sharing /and/ opening up options like this to terminally ill patients we can (a) save individual lives and (b) speed up development and refinement of new treatments to benefit everyone. The problem is that the incentives we have in place treat a cancer death as acceptable, while a treatment-related death is unacceptable for researchers, doctors and drug companies (unless they are shielded by layers of clinical-trial bureaucracy or years of standard practice). The result is that the course of treatment doesn't properly weigh the different sources of risk. Whether the goal is quality-adjusted life years for an individual patient or faster development of effective and safe treatments, the current system is way too conservative. [1] http://www.eurekalert.org/aaasnewsroom/2016/webcast/?b=38 http://www.eurekalert.org/aaasnewsroom/2016/webcast/?b=38
  - nonbel 11y ago
    For what it's worth, I used to say I would take some experimental treatment when the time came. Not after doing research myself and seeing first hand what "experimental" really means when it comes to medicine. It means: no one has any way of really knowing what is going on. For example, 1) There will be some studies where a measurement was higher in the treatment group compared to controls, but it is not 100% clear what combination of things is actually being measured. 2) There will be other studies you hear about that got different results, but didn't get published because publishing "negative results" is discouraged and bad for careers. 3) The criteria for publishing a positive result is a p-value below an arbitrary threshold, and most people researching medical treatments really do not understand the meaning of a p-value to begin with. There are all sorts of myths like it is the probability the treatment didn't work, etc. So (at least the implementation of) the basic criteria used to judge success is fatally flawed. It is quite scary and I don't see anything I can do about it but make people aware there is a problem here.
dschiptsov 11y ago
Theory holds that mutations are random and each cancer process is different.
marckemil 11y ago
As was pointed out before, those are unpublished results. We cannot extract any significant information from this article. For example, in many early phase trials, the standard treatment is often given WITH the new drug (or vaccine), so we'd have to know the response rate of the control group. As other pointed out, blood cancers are very different than solid tumors -- they've historically been easier to treat. That's probably due to the tumor micro environnement that makes solid tumor a very different process. To put simply, I would not assume for a second that outcomes for blood cancers can be replicated for solid tumors. Immunotherapy is all the rage in the cancer world right now. It resonates with patient that "their own bodies can destroy cancer". It's almost romantic. Kinda like when anti-angiogenesis drugs were all the rage a few years ago... The "cancer vaccine" has been tried many times before. Pretty much every time the cancer finds a way around it. Sipuleucel-T is a commercially available cancer vaccine for prostate cancer. It adds a few months for $$$, but newer, non-vaccine treatments are now doing better. We're unlikely to find "a" cure for cancer; we'll eventually find "cures" for cancer, but it will be small, incremental steps. In the meantime I'll go back to my clinic and continue to enrol patients on clinical trials
- petra 11y ago
  What about extremely early and accurate diagnostic screening , which can offer 0% or very close to 0% false negatives(and ~30% false positives, like quanterix talks about), followed by a full panel of the relevant proteins ,guiding to the correct,low dose highly targeted chemo therapies ? Considering that some results of treating early(by today's standards <2-3mm tumor) we can get to something like 95%-98% 5-years cancer free rates(while suffering some side effects), in breast cancer - it seems possible to make cancer a low-risk ,low-pain disease - as long as you do your regular checkups. Right ?
  - marckemil 11y ago
    Cancer research is not an easy field and many are better than me in that regard. But food for thoughts: A screening test with 30% false positive is not a great test. One in three test takers would be positive, requiring more investigations (likely many more). Let's say 1000 asymptomatic person take the test, 300 will test positive. Physicians then have to investigate thoroughly those patients. $$$ for those tests, hours of work missed, and very importantly patient anxiety and potential harm (a prostate biopsy, for example, is not trivial and people can die from that) of those 1000 people screened, 1 has the disease. With a 0% false negative rate, we catch it. Because of the test, it was caught early. Have we really changed his outcomes? would he have discovered it by himself a few weeks later, not impacting any of his treatments? The convention of "catching cancer early will make it easier to cure" is not always true. In the meantime, we've had to put 300 people through useless agressive investigations... Moreover, 0% false negative would be revolutionary. -- 0% and 100% are extremely rare in medicine. Anyhow, screening, especially its drawbacks is one of the most complex concept to explain. For genotyping and targeted treatments: it's been tried but we're still not there yet. The papers coming out are disappointing in that regard.

130 points by tempestn 11y ago

Why are all the gene-based cancer breakthroughs I've seen in the news for blood diseases? Is it easier to manipulate genes in blood?

teekert 11y ago
I think it is because in blood drugs and gene based treatments are the only option, surgery is simply not an option. This has always spurred the blood cancer field to take greater risks, the all or nothing approach.
- erkkie 11y ago
  Surgery is an option, namely bone-marrow transplants. The reason blood cancers are first with these techniques boils down to having better known antigen targets to target compared to solid tumors where known antigens have more cross reactivity to other tissues (so less specificity, more side-effects).
  - carbocation 11y ago
    Despite the word "transplant", bone marrow transplants are not done surgically; they are done by infusion of donor cells into the bloodstream. Then, the cells seek out their own niche and engraft.
    - erkkie 11y ago
      Good point, you're right, not surgery, more like an (significantly invasive) procedure. Still good to differentiate from "giving a drug".
- pacap 11y ago
  From what I remember, these blood cancer have an antigen, CD13 or something, which is unique to them - no other body part has it, making it easy to target them. Otherwise, you get the side effect of destroying your own body, the case of a woman a few years ago, who died having her lungs destroyed by immunotherapy. Lungs had the same antigen. This morning I read something hopeful in this direction - UCSF researchers designed an AND gate, so now they could trigger a T cell attack only when 2 specific antigens are present, making it much more reliable. And I could imagine these can be chained, further narrowing it down. It needs genetic sequencing to isolate. https://www.ucsf.edu/news/2016/01/401471/tricked-out-immune-cells-could-attack-cancer-spare-healthy-cells https://www.ucsf.edu/news/2016/01/401471/tricked-out-immune-... At the moment this is a terrible manual and time consuming process, so it is expensive.
  - erkkie 11y ago
    This is also why a combination of engineered T-cells and immune checkpoint inhibitors is a really winning combo. http://www.theguardian.com/society/2015/jun/01/paradigm-shift-hailed-in-treatment-of-lung-cancer http://www.theguardian.com/society/2015/jun/01/paradigm-shif...
    - AstralStorm 11y ago
      Immune checkpoint (fancy name that, you probably mean anti-autoimmune system) inhibitors main problem is the very high risk of autoimmune disorders that are hard or impossible to treat. Just toggling the suppressor will not kill clonal cells already in circulation, and those can last a long, long time, or even a lifetime. If you're unlucky, you will also get "broken" immune memory cells - which also last for life. Trading cancer for SLE or rheumatoidal arthritis etc.
forgotpwagain 11y ago
In general, blood cancers are more accessible than solid tumors. With blood cancers, the majority of the cancer cells are in the blood or in very well perfused tissues (bone marrow, spleen, thymus, etc), meaning that drugs/treatments can get to the targets very easily. With solid tumors, you have to deal with the complexities of the tumor microenvironment. The tumor microenvironment is the complex environment of the cancer tumor tissue. Of particular note, decreased lymphatic drainage, increased connective tissue, and aberrant angiogenesis (growth of new blood vessels) create very high interstitial fluid pressures within the tumor, limiting the ability of drugs or cells to penetrate within the tumor and "work their magic" by reaching the cells/target molecules of interest, etc. Blood cancers are a good proof-of-principle for many cancer therapies; translation to solid tumors is difficult (see challenges with CAR-T cell immunotherapy). As for gene manipulation in blood--yes, it is relatively easy to manipulate genes in blood. Hematopoetic Stem Cells (which differentiate into all different kinds of blood cells) can be withdrawn without too much difficulty, manipulated in the lab, and then reinjected into the patient.
- agumonkey 11y ago
  Pardon the naive question, I don't know how localized therapies are today, but hasn't there been research into developing fake foreign capillaries to be implanted non invasively to deliver drugs right on target ? ps: I remember seeing more 'barbaric' version of the idea, namely metal pipes planted in the patient as a direct path. I was wondering about something more organic.
  - forgotpwagain 11y ago
    I'm not an expert, but I think there's been a variety of attempts for vascular renormalization--to restore the normal flow of vessels to allow for drug delivery, etc. Rakesh Jain's lab (at MGH) is a big player in this field and is worth looking up if you're interested. I'm not personally familiar with work in developing capillary devices, but it wouldn't surprise me at all if this was an approach under development--it certainly makes a lot of sense.
    - 11y ago

teekert 11y ago

I really appreciate the down-to-earth-ness of this interview, this man is being very honest. It's good not to create false hope and present cancer immunotherapy (yet perhaps) as the thing that will cure any cancer. However, it is the only real curative treatment next to surgery and really the only treatment that can cure metastatic cancer. At the moment though, only in small percentage of people with specific cancers (mostly melanoma, skin cancers.) So there certainly is reason to be excited, the cancer field is all over this at the moment so advances in the near future can be expected.

dang 11y ago
> the down-to-earth-ness of this interview That would be the interview at http://www.bbc.com/news/health-35585571 http://www.bbc.com/news/health-35585571. We changed the URL to a text version of the story.
forgotpwagain 11y ago
The method by which vaccinations work is immunological. I think the most exciting frontier in cancer biology is prophylactic (preventative) vaccination. If we are able to develop effective vaccines against cancers, that will very much change the game. This is currently a research frontiers area--but in 10-20 years, I believe that we will have made significant inroads on it.
- teekert 11y ago
  Since every cancer is different in the markers it displays, I think that is unlikely to happen. It would mean an insane amount of vaccinations and the assumption that they have none to acceptable side effects.
  - mbreese 11y ago
    Not to mention the risk for an auto-immune complication... because the cancer is just slightly different from "self", any immune response will have a very high risk for auto-immune recognition. That's why CAR-T treatments are considered only in the cases where all other options have been exhausted.

deleted 11y ago

[deleted]

nonbel 11y ago

"The findings are yet to be published and reviewed." Are people really ok with this practice of researchers talking about their discoveries without having shared the methods and data (I don't care so much about the review aspect)? I'm certainly not, but apparently many think this is acceptable for some reason because I don't see any pushback.

tominous 11y ago
I'm biased. My wife was diagnosed with metastatic cancer 6 months ago. With current standard treatments there is a 3-year survival rate of practically zero, so to me the most important thing is getting new effective treatments developed and brought into clinical practice as soon as possible. I haven't seen the presentation about the study (a related news briefing is here [1]) so I don't know whether you're correct to say that the researchers haven't shared their methods and data. They seem quite happy to share technical details at the news briefing. However, regardless of that, I still think it is a good thing if researchers talk about their findings at an early stage, especially if the findings are as dramatic and positive as these. If a treatment is available and you have patients out there dying with no other options, then it is just wrong to hide that away. In my opinion we treat these things far too cautiously. It is not optimal for the individual and it is not optimal for society. By sharing /and/ opening up options like this to terminally ill patients we can (a) save individual lives and (b) speed up development and refinement of new treatments to benefit everyone. The problem is that the incentives we have in place treat a cancer death as acceptable, while a treatment-related death is unacceptable for researchers, doctors and drug companies (unless they are shielded by layers of clinical-trial bureaucracy or years of standard practice). The result is that the course of treatment doesn't properly weigh the different sources of risk. Whether the goal is quality-adjusted life years for an individual patient or faster development of effective and safe treatments, the current system is way too conservative. [1] http://www.eurekalert.org/aaasnewsroom/2016/webcast/?b=38 http://www.eurekalert.org/aaasnewsroom/2016/webcast/?b=38
- nonbel 11y ago
  For what it's worth, I used to say I would take some experimental treatment when the time came. Not after doing research myself and seeing first hand what "experimental" really means when it comes to medicine. It means: no one has any way of really knowing what is going on. For example, 1) There will be some studies where a measurement was higher in the treatment group compared to controls, but it is not 100% clear what combination of things is actually being measured. 2) There will be other studies you hear about that got different results, but didn't get published because publishing "negative results" is discouraged and bad for careers. 3) The criteria for publishing a positive result is a p-value below an arbitrary threshold, and most people researching medical treatments really do not understand the meaning of a p-value to begin with. There are all sorts of myths like it is the probability the treatment didn't work, etc. So (at least the implementation of) the basic criteria used to judge success is fatally flawed. It is quite scary and I don't see anything I can do about it but make people aware there is a problem here.

dschiptsov 11y ago

Theory holds that mutations are random and each cancer process is different.

marckemil 11y ago

As was pointed out before, those are unpublished results. We cannot extract any significant information from this article. For example, in many early phase trials, the standard treatment is often given WITH the new drug (or vaccine), so we'd have to know the response rate of the control group. As other pointed out, blood cancers are very different than solid tumors -- they've historically been easier to treat. That's probably due to the tumor micro environnement that makes solid tumor a very different process. To put simply, I would not assume for a second that outcomes for blood cancers can be replicated for solid tumors. Immunotherapy is all the rage in the cancer world right now. It resonates with patient that "their own bodies can destroy cancer". It's almost romantic. Kinda like when anti-angiogenesis drugs were all the rage a few years ago... The "cancer vaccine" has been tried many times before. Pretty much every time the cancer finds a way around it. Sipuleucel-T is a commercially available cancer vaccine for prostate cancer. It adds a few months for $$$, but newer, non-vaccine treatments are now doing better. We're unlikely to find "a" cure for cancer; we'll eventually find "cures" for cancer, but it will be small, incremental steps. In the meantime I'll go back to my clinic and continue to enrol patients on clinical trials

petra 11y ago
What about extremely early and accurate diagnostic screening , which can offer 0% or very close to 0% false negatives(and ~30% false positives, like quanterix talks about), followed by a full panel of the relevant proteins ,guiding to the correct,low dose highly targeted chemo therapies ? Considering that some results of treating early(by today's standards <2-3mm tumor) we can get to something like 95%-98% 5-years cancer free rates(while suffering some side effects), in breast cancer - it seems possible to make cancer a low-risk ,low-pain disease - as long as you do your regular checkups. Right ?
- marckemil 11y ago
  Cancer research is not an easy field and many are better than me in that regard. But food for thoughts: A screening test with 30% false positive is not a great test. One in three test takers would be positive, requiring more investigations (likely many more). Let's say 1000 asymptomatic person take the test, 300 will test positive. Physicians then have to investigate thoroughly those patients. $$$ for those tests, hours of work missed, and very importantly patient anxiety and potential harm (a prostate biopsy, for example, is not trivial and people can die from that) of those 1000 people screened, 1 has the disease. With a 0% false negative rate, we catch it. Because of the test, it was caught early. Have we really changed his outcomes? would he have discovered it by himself a few weeks later, not impacting any of his treatments? The convention of "catching cancer early will make it easier to cure" is not always true. In the meantime, we've had to put 300 people through useless agressive investigations... Moreover, 0% false negative would be revolutionary. -- 0% and 100% are extremely rare in medicine. Anyhow, screening, especially its drawbacks is one of the most complex concept to explain. For genotyping and targeted treatments: it's been tried but we're still not there yet. The papers coming out are disappointing in that regard.