8 ms·

Unconventional Case Study of Neoadjuvant Oncolytic Virotherapy for Breast Cancer

170 points by Amezarak 2y ago

v3ss0n 2y ago
Really facinating. Using Virus to cure cancer. Just like from I Am Legend movie. ``` The movie opens with a scene of Dr. Alice Krippin, who created the virus to cure cancer, discussing her work. Krippin states that 10,009 clinical trials were completed and all of the participants were successfully cured. However, it is later discovered that the virus is lethal. A genetically modified measles virus kills most humans and turns some people into mutant creatures. ``` I hope it wont end up like `I Am Legend` movie. How long those research are being there , the movie script is a coincidence?
- aplummer 2y ago
  This is the real world where science has redefined life expectancy and saves millions of lives a year, not a fictional will smith movie.
- folli 2y ago
  That's not the point, oncolytic viruses have been researched since the 1950s. The fascinating thing is that this has been done in a self-experiment with viruses grown in her own lab.
ldayley 2y ago
This is a fascinating area of research in general, but what’s notable here is that the researcher herself was afflicted with the tumors and self-administered these experimental treatments!
folli 2y ago
The science is not new, but the reason why this paper is raising some eyebrows is the following: Institutional Review Board Statement This is a case of self-experimentation. As such, it does not require ethics committee review [33,34,35]. The study was feasible only due to the unique situation in which the patient was also an expert virologist. The patient was fully aware of her illness as well as of available therapies, and as a scientist in the field of virology, she was aware of the potential of oncolytic virotherapy. After two recurrences of the same tumour, she wanted to try an innovative approach in a scientifically sound way. Her oncologists (the leading oncologists in Croatia for breast cancer) accepted to monitor the progress of the treatment, primarily with the aim of discontinuing the injections and intervening with conventional therapy if there were untoward effects or if the tumour progressed.
- kortex 2y ago
  Definitely eyebrow raising but I'm always a fan of a bit of "mad scientist" self-experimentation (within reason), whether it be Barry Marshall chugging H. pylori or Thought Emporium giving himself lactase gene therapy.
- Loughla 2y ago
  I think it's pretty great. Put your mouth where your money is sort of thing.
- noddleah 2y ago
  Agree. This is one of the first things I thought, and while I'm not super well versed in the processes behind getting clinical experiments approved, I can see how the data might not account for confounders that you'd see in a traditional clinical study
pazimzadeh 2y ago
> The patient, who is also an expert virologist, anticipating that the recurrent tumour would be of TNBC phenotype for which therapies of only limited efficacies exist, informed her oncologists that she was going to treat this tumour by the i.t. administration of viruses similar to oncolytic viruses (that were in clinical development for BC) before undergoing any other treatment. Really smart to use the viral therapy before chemotherapy, since chemotherapy dampens the immune system, and the immune system probably promotes further tumor clearance once the tumors soften and are full of viruses.
- trhway 2y ago
  Yes, the catch-22 mentioned in the article is that the clinical studies are done on late stage patients with usually at that point severely damaged immune system which of course wouldn’t produce desired effect especially if it is about using virus to cause flooding of the tumor with the immune response cells and not about virus directly attacking cancer cells. Also in the metastatic late stage one can imagine it isn’t really possible to inject each tumor.
- CipherThrowaway 2y ago
  This is a big simplification. 1. The interaction between oncolytic virotherapy and host immunity is complex. Consider that oncolytic viruses are also targeted by the immune system. 2. Oncolytic viruses that directly destroy cancer cells may not depend on a host immune response at all for therapeutic effectiveness. 3. There are many common chemotherapy agents that enhance anti-tumor immunity. For example, 5FU is understood to enhance anti-tumor response and activate the p53 pathway. 4. Immunosuppressive chemotherapies can still enhance anti-tumor immunity by changing the tumor microenvironment. This is one of the principles behind combined chemo-immunotherapy regimes in treatment of solid tumors. 5. Some immune cells promote tumor growth and suppress anti-tumor immunity. Tumor associated myeloid cells are one example of an immune cell suppressed by chemotherapy that promote tumor survival. This is just scratching the surface of some of the complexities here. In general, cancer and cancer treatment are incredibly complex with massive variation not just between types of cancer but within individual cancers themselves. Oncology does not lend itself to simplistic thinking.
Galatians4_16 2y ago
Cool, but how can we hack this?
- seism 2y ago
  With a Hackathon! And a couple of cohorts, just to be on the safe side.
Filligree 2y ago
So the treatment worked, and she appears to be recovered from what might otherwise have been treatment-resistant, fatal cancer. But she was only able to do so because of having the skill and access needed to self-administer the cure. How many people die every year because we don't dare risk any deaths from uncertain treatments like these? Sure, they aren't ever going to be perfect, but- what's the net?
- admissionsguy 2y ago
  For this reason I have mixed feelings concerning Richard Scolyer’s glioblastoma treatment. On one hand it’s great that he has possibly found something that works and will in time become the new standard of care. At the same time it is disturbing that thousands of patients who are not renowned scientists have to die without a chance to try the same treatment.
  - teyc 2y ago
    You make a good point. Could there be a case for new ethical considerations to be made. The issue is patients are very vulnerable and no one really knows how bad the downside may be. A prolonged agonising or disabling death can be far worse.
  - melling 2y ago
    It is disturbing. For some reason it’s not disturbing enough that we spend more to try and cure these diseases. The Last Lecture was given almost 20 years ago. Pancreatic cancer is just as deadly today. https://youtu.be/ji5_MqicxSo?si=bn6VBPaWraUfO-zC https://youtu.be/ji5_MqicxSo?si=bn6VBPaWraUfO-zC
- daveguy 2y ago
  There is a lot of leeway (in the US) for treatment of terminal diseases with the Right to Try Act: https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try https://www.fda.gov/patients/learn-about-expanded-access-and...
  - 2y ago
nyanpasu64 2y ago
Who was injecting the tumor? I'm squeamish enough I can't imagine being able to inject myself, let alone into a tumor...
- sfink 2y ago
  I self-injected weekly for half a year for a much more mild and mundane reason (immunotherapy). It sucked. Because I was doing it at home and not under observation, the dose schedule was way more conservative, so I'm not sure if it ended up saving any time at all despite the long drive to the clinic and the wait afterward. And stabbing yourself—even in the leg, as in my case—is not an easy thing to do. I thought it would get easier over time, and maybe it did a little, but there was a lot of variance and even towards the end some days it took me 10 minutes to psych myself up enough to do it. (Feeling monumentally foolish, but still not able to stick it in.) Amusingly: after I switched to the conventional therapy of being injected by a nurse at a clinic, the nurse said she could never do it to herself. And she injects on the order of 100 patients per week! Self-injecting into a breast... I can't even imagine. I guess the life-threatening nature, and not having an alternative, are powerful forces.
TexanFeller 2y ago
This is particularly interesting to me because someone very close to me is in treatment for fairly advanced BC. While it might not be in time to help her, it’s exciting that someone is finally trying something very different than the normal approaches. Breast cancer treatment has continually advanced, but with only slow incremental progress, and where treatment is now still feels extremely primitive. In addition to having potentially life threatening or quality of life destroying side effects most normal treatments provide only moderate increase in lifespan unless you’re lucky enough to have early chemo clear it 100%. As I understand it hormone blocker therapy and the *mab drugs used in stage four usually lose effectiveness as the cancer mutates, such as to not depend on the presence of hormones to grow.
Svoka 2y ago
Honestly, this is the first time I thought I was reading thriller novel, not a paper abstract. Fascinating topic, I wonder where it would go. How does medic science bode with such "experiments"?
DantesKite 2y ago
It’s interesting comparing the comments here to Twitter where there’s been a lot of discussion about the ethics of this (as in she shouldn’t have done this for some ethical reason that is never quite elucidated in detail, other than it’s wrong to do). In contrast, many comments here are talking about the ethics of not having this approach more broadly available, which is fairly optimistic for Hacker News. Or maybe it’s just that a subsection of bio-ethicists on Twitter have oddly shaped moral values.
- alphazard 2y ago
  Twitter has the full gambit of ideologies, and the ethical models that those precommit a person to. It's amusing to watch the mental gymnastics required to come down against the common sense view that no one was negatively affected by her actions, and she personally benefited, and so it must be okay. I think rational consequentialism is a common stance here on HN. e.g. I would be better off having access to this treatment (on my own terms of course), and other people having access to it would not negatively affect me, so I'm in favor.
- khafra 2y ago
  The most prominent bioethicist tweet, from @Strangviruslab, has over twice as many QT's as likes. It's among the biggest pile-ons I've ever seen on twitter.
password4321 2y ago
In a similar vein yesterday: Four Thieves Vinegar Collective – Harm Reduction for the Living - https://news.ycombinator.com/item?id=41474080 https://news.ycombinator.com/item?id=41474080 - Sep 2024 (186 comments) "Right to Repair–for Your Body. ... enabling access to medicines and medical technologies to those who need them but don’t have them" DEFCON talk 2 days ago: https://www.youtube.com/watch?v=5rQklSmI_F0 https://www.youtube.com/watch?v=5rQklSmI_F0
markus92 2y ago
The really interesting part of this study (besides the obvious self-experimentation) is that she underwent subtype conversion from TN to HER2+ tumor and thus could use Trastuzumab.
- CipherThrowaway 2y ago
  The development of PD-L1 expression was also interesting.

170 points by Amezarak 2y ago

Really facinating. Using Virus to cure cancer. Just like from I Am Legend movie. ``` The movie opens with a scene of Dr. Alice Krippin, who created the virus to cure cancer, discussing her work. Krippin states that 10,009 clinical trials were completed and all of the participants were successfully cured. However, it is later discovered that the virus is lethal. A genetically modified measles virus kills most humans and turns some people into mutant creatures. ``` I hope it wont end up like `I Am Legend` movie. How long those research are being there , the movie script is a coincidence?

aplummer 2y ago
This is the real world where science has redefined life expectancy and saves millions of lives a year, not a fictional will smith movie.
folli 2y ago
That's not the point, oncolytic viruses have been researched since the 1950s. The fascinating thing is that this has been done in a self-experiment with viruses grown in her own lab.

ldayley 2y ago

This is a fascinating area of research in general, but what’s notable here is that the researcher herself was afflicted with the tumors and self-administered these experimental treatments!

folli 2y ago

The science is not new, but the reason why this paper is raising some eyebrows is the following: Institutional Review Board Statement This is a case of self-experimentation. As such, it does not require ethics committee review [33,34,35]. The study was feasible only due to the unique situation in which the patient was also an expert virologist. The patient was fully aware of her illness as well as of available therapies, and as a scientist in the field of virology, she was aware of the potential of oncolytic virotherapy. After two recurrences of the same tumour, she wanted to try an innovative approach in a scientifically sound way. Her oncologists (the leading oncologists in Croatia for breast cancer) accepted to monitor the progress of the treatment, primarily with the aim of discontinuing the injections and intervening with conventional therapy if there were untoward effects or if the tumour progressed.

kortex 2y ago
Definitely eyebrow raising but I'm always a fan of a bit of "mad scientist" self-experimentation (within reason), whether it be Barry Marshall chugging H. pylori or Thought Emporium giving himself lactase gene therapy.
Loughla 2y ago
I think it's pretty great. Put your mouth where your money is sort of thing.
noddleah 2y ago
Agree. This is one of the first things I thought, and while I'm not super well versed in the processes behind getting clinical experiments approved, I can see how the data might not account for confounders that you'd see in a traditional clinical study

pazimzadeh 2y ago

> The patient, who is also an expert virologist, anticipating that the recurrent tumour would be of TNBC phenotype for which therapies of only limited efficacies exist, informed her oncologists that she was going to treat this tumour by the i.t. administration of viruses similar to oncolytic viruses (that were in clinical development for BC) before undergoing any other treatment. Really smart to use the viral therapy before chemotherapy, since chemotherapy dampens the immune system, and the immune system probably promotes further tumor clearance once the tumors soften and are full of viruses.

trhway 2y ago
Yes, the catch-22 mentioned in the article is that the clinical studies are done on late stage patients with usually at that point severely damaged immune system which of course wouldn’t produce desired effect especially if it is about using virus to cause flooding of the tumor with the immune response cells and not about virus directly attacking cancer cells. Also in the metastatic late stage one can imagine it isn’t really possible to inject each tumor.
CipherThrowaway 2y ago
This is a big simplification. 1. The interaction between oncolytic virotherapy and host immunity is complex. Consider that oncolytic viruses are also targeted by the immune system. 2. Oncolytic viruses that directly destroy cancer cells may not depend on a host immune response at all for therapeutic effectiveness. 3. There are many common chemotherapy agents that enhance anti-tumor immunity. For example, 5FU is understood to enhance anti-tumor response and activate the p53 pathway. 4. Immunosuppressive chemotherapies can still enhance anti-tumor immunity by changing the tumor microenvironment. This is one of the principles behind combined chemo-immunotherapy regimes in treatment of solid tumors. 5. Some immune cells promote tumor growth and suppress anti-tumor immunity. Tumor associated myeloid cells are one example of an immune cell suppressed by chemotherapy that promote tumor survival. This is just scratching the surface of some of the complexities here. In general, cancer and cancer treatment are incredibly complex with massive variation not just between types of cancer but within individual cancers themselves. Oncology does not lend itself to simplistic thinking.

Galatians4_16 2y ago

Cool, but how can we hack this?

seism 2y ago
With a Hackathon! And a couple of cohorts, just to be on the safe side.

Filligree 2y ago

So the treatment worked, and she appears to be recovered from what might otherwise have been treatment-resistant, fatal cancer. But she was only able to do so because of having the skill and access needed to self-administer the cure. How many people die every year because we don't dare risk any deaths from uncertain treatments like these? Sure, they aren't ever going to be perfect, but- what's the net?

admissionsguy 2y ago
For this reason I have mixed feelings concerning Richard Scolyer’s glioblastoma treatment. On one hand it’s great that he has possibly found something that works and will in time become the new standard of care. At the same time it is disturbing that thousands of patients who are not renowned scientists have to die without a chance to try the same treatment.
- teyc 2y ago
  You make a good point. Could there be a case for new ethical considerations to be made. The issue is patients are very vulnerable and no one really knows how bad the downside may be. A prolonged agonising or disabling death can be far worse.
- melling 2y ago
  It is disturbing. For some reason it’s not disturbing enough that we spend more to try and cure these diseases. The Last Lecture was given almost 20 years ago. Pancreatic cancer is just as deadly today. https://youtu.be/ji5_MqicxSo?si=bn6VBPaWraUfO-zC https://youtu.be/ji5_MqicxSo?si=bn6VBPaWraUfO-zC
daveguy 2y ago
There is a lot of leeway (in the US) for treatment of terminal diseases with the Right to Try Act: https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try https://www.fda.gov/patients/learn-about-expanded-access-and...
- 2y ago

nyanpasu64 2y ago

Who was injecting the tumor? I'm squeamish enough I can't imagine being able to inject myself, let alone into a tumor...

sfink 2y ago
I self-injected weekly for half a year for a much more mild and mundane reason (immunotherapy). It sucked. Because I was doing it at home and not under observation, the dose schedule was way more conservative, so I'm not sure if it ended up saving any time at all despite the long drive to the clinic and the wait afterward. And stabbing yourself—even in the leg, as in my case—is not an easy thing to do. I thought it would get easier over time, and maybe it did a little, but there was a lot of variance and even towards the end some days it took me 10 minutes to psych myself up enough to do it. (Feeling monumentally foolish, but still not able to stick it in.) Amusingly: after I switched to the conventional therapy of being injected by a nurse at a clinic, the nurse said she could never do it to herself. And she injects on the order of 100 patients per week! Self-injecting into a breast... I can't even imagine. I guess the life-threatening nature, and not having an alternative, are powerful forces.

TexanFeller 2y ago

This is particularly interesting to me because someone very close to me is in treatment for fairly advanced BC. While it might not be in time to help her, it’s exciting that someone is finally trying something very different than the normal approaches. Breast cancer treatment has continually advanced, but with only slow incremental progress, and where treatment is now still feels extremely primitive. In addition to having potentially life threatening or quality of life destroying side effects most normal treatments provide only moderate increase in lifespan unless you’re lucky enough to have early chemo clear it 100%. As I understand it hormone blocker therapy and the *mab drugs used in stage four usually lose effectiveness as the cancer mutates, such as to not depend on the presence of hormones to grow.

Svoka 2y ago

Honestly, this is the first time I thought I was reading thriller novel, not a paper abstract. Fascinating topic, I wonder where it would go. How does medic science bode with such "experiments"?

DantesKite 2y ago

It’s interesting comparing the comments here to Twitter where there’s been a lot of discussion about the ethics of this (as in she shouldn’t have done this for some ethical reason that is never quite elucidated in detail, other than it’s wrong to do). In contrast, many comments here are talking about the ethics of not having this approach more broadly available, which is fairly optimistic for Hacker News. Or maybe it’s just that a subsection of bio-ethicists on Twitter have oddly shaped moral values.

alphazard 2y ago
Twitter has the full gambit of ideologies, and the ethical models that those precommit a person to. It's amusing to watch the mental gymnastics required to come down against the common sense view that no one was negatively affected by her actions, and she personally benefited, and so it must be okay. I think rational consequentialism is a common stance here on HN. e.g. I would be better off having access to this treatment (on my own terms of course), and other people having access to it would not negatively affect me, so I'm in favor.
khafra 2y ago
The most prominent bioethicist tweet, from @Strangviruslab, has over twice as many QT's as likes. It's among the biggest pile-ons I've ever seen on twitter.

password4321 2y ago

In a similar vein yesterday: Four Thieves Vinegar Collective – Harm Reduction for the Living - https://news.ycombinator.com/item?id=41474080 https://news.ycombinator.com/item?id=41474080 - Sep 2024 (186 comments) "Right to Repair–for Your Body. ... enabling access to medicines and medical technologies to those who need them but don’t have them" DEFCON talk 2 days ago: https://www.youtube.com/watch?v=5rQklSmI_F0 https://www.youtube.com/watch?v=5rQklSmI_F0

markus92 2y ago

The really interesting part of this study (besides the obvious self-experimentation) is that she underwent subtype conversion from TN to HER2+ tumor and thus could use Trastuzumab.

CipherThrowaway 2y ago
The development of PD-L1 expression was also interesting.