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mRNA Cancer Vaccine Reprograms Immune System to Tackle Glioblastoma in 48 Hours

pompino
45 replies
10h57m

One big problem is the FDA's slowness regarding treatments for otherwise fatal diseases like GBM.

What do you mean by slowness? They can't skip all the safety stuff!

px43
19 replies
10h32m

Why is it that so many people need to die in the name of safety?

pompino
16 replies
10h17m

Because you can't honestly presume to know the outcome of a clinical trial of an untested product.

FeepingCreature
12 replies
9h21m

So run the clinical trial, advertise the product as untested and dangerous-to-lethal in the meantime, and let people make their own choices?

bartekrutkowski
7 replies
9h13m

Smoking is already advertised as dangerous-to-lethal and look how effective it is in preventing people from smoking.

In huge oversimplification some crazy or fraudulent people will claim it cures blindness or cold sores, some other people will believe them and will have to deal with the real danger-to-lethal consequences, with the rest of society paying for their medical care afterwards.

defrost
6 replies
8h55m

Smoking is already advertised as dangerous-to-lethal and look how effective it is in preventing people from smoking.

Pretty effective.

In Australia throwing a few diseased lungs on the packs and increasing public awareness has seen usage drop from 35% of the population in 1980 to 11% today.

Not all the drop is purely related to advertising, price increases and restricting sale to out of sight locked access in shops have also helped.

https://www.tobaccoinaustralia.org.au/chapter-1-prevalence/1...

mewpmewp2
4 replies
8h8m

From another perspective it took massive change in generations and over 40 years of campaigning and it is still a problem for the 11 percent.

defrost
3 replies
7h59m

Knocking back smoking by two thirds has saved billions for the national health system.

On the books, totally worth it.

mewpmewp2
1 replies
6h32m

Sure, but imagine doing the same effort that likely requires critical mass for actual adaption on small obscure medicines and illnesses.

FeepingCreature
0 replies
2h45m

Are they addictive? Then regulate them as addictive drugs.

Are they not addictive? Then it seems a stretch to compare them to cigarettes.

b800h
0 replies
3h55m

And cost billions in state pensions. I'm not suggesting that's any sort of counterargument but the costs should possibly be offset against other types of end-of-life care.

bartekrutkowski
0 replies
2h43m

Sure it's effective if you're looking at the reduction rate of existing number alone. But reverse the problem and the very big effort of warning about dangerous-to-lethal stuff still doesn't stop 11% of people from doing so. That's quite bad, when you think about going from zero (you can't willy-nilly use untested medicine) to 11% of the society.

jddj
2 replies
8h56m

I have a new drug. It's called aceite deserpiente.

It's a cure for lyme disease, impotence, ALS, chronic fatigue, cancer and aging. Trials are pending but what are you waiting for, do you want to die for lack of trying? 10k/dose.

ben_w
0 replies
8h4m

aceite deserpiente

Nice name choice for your example; I was thinking of paracetamoxyfrusebendroneomycin myself, yours is better.

FeepingCreature
0 replies
2h47m

See, the thing is, I can just choose not to buy it.

hackerlight
2 replies
8h27m

You've proposed a nonsensical epistemic framework. Knowing isn't binary.

You should have a probability distribution over possibilities, based on your experience with similar drugs, expert hunches and animal trials. You then use that to estimate risks and benefits. Then compare this risk-reward profile with the risks of doing nothing -- in this case, near certain death from brain cancer.

This "can't presume to know" framework is just sophistry. And I think deep down you know that, if you had a death sentence from brain cancer you'd be begging them to let you in the trial even if they "couldn't presume to know".

haldujai
1 replies
8h12m

You’re missing that we have treatments with known risk/benefits vs research treatment X with undefined risk and reward.

It’s extremely challenging if not impossible to obtain informed consent in this situation.

We’ve been through this before where a fancy new treatment with promising early/lab results usurped conventional therapy only to later be found inferior.

Earlier TKIs and NSCLC are a recent example that comes to mind.

hackerlight
0 replies
7h58m

It's not undefined, though. That's the point I'm getting at. There is no binary of known and unknown. A tentative picture exists based on animal trials and expert judgment. That tentative picture informs an estimation of the risk to reward profile which is then the basis for an informed decision.

This is decision making under uncertainty. It's bad practice to say that uncertainty always means "don't do it".

nickpp
1 replies
9h14m

Because nobody's counting deaths from "not doing stuff". Everybody counts deaths from actions done (things built, products sold, meds taken) but nobody's counting losses from things (like meds) simply missing.

In effect we regulated doing stuff so much in the name of safety that we ended up in an infinite "analysis paralysis" mode where the you have to absolutely prove zero harm from new products/services while completely ignoring the harm the current status quo does.

See current debates over AI, self-driving cars, and of course, meds.

tga_d
0 replies
1h32m

What do you mean "nobody's counting"? Excess mortality from delayed or denied treatments are measured all the time in medical research. How do you think these drugs get made in the first place? We just had a pandemic where a calculated decision was made that the small risk of myocarditis was massively outweighed by the benefits of mass vaccination. When was the last time you saw a drug ad that didn't list potentially fatal or debilitating side effects? "We need something to solve problem X even if it carries risk Y" is absolutely par for the course.

evandijk70
15 replies
8h38m

Not just safety, but also effectiveness. FDA checks whether the trial(s) to prove the drugs effectiveness were run correctly (eg. the randomization, the control group, etc.), if the statistical analysis was done right, if the endpoints are appropriate (response to treatment is not always objective) etc. etc.

The FDA (and EMA in Europe) are the only thing that protects desperate patients from fraudsters, charlatans and pharma-companies just looking for a return on their investment.

bhickey
12 replies
7h46m

Ideally this is what would happen. In practice there have been very public failures in being overly cautious and aggressive.

While Aduhelm reduces Aβ it has no clinically significant effect. Still, the FDA approved it. Mercifully it'll be discontinued in November.

The covid vaccine represented a huge policy failure by the FDA. While people in nursing homes died in droves we got small clinical trials. When you've got 90 year olds in a congregate setting facing a 50% chance of death, maybe it's time to stop pretending thalidomide may be lurking around every corner. The pediatric trials were just as bad. Due to their sizing it was statistically impossible to detect rare adverse effects. Yet, vaccination was delayed for children while these fruitless trials ran.

In my own experience I had a low cost, high throughput covid testing protocol ready to go in early April 2020. It took the FDA until August 2020 to provide templates and another month to grant emergency use authorization. We could've drastically ramped up testing when it was needed most of the FDA has treated an emergency like an emergency.

_heimdall
10 replies
6h34m

Is it your opinion that trials for the Covid vaccine should have been skipped to vaccinate people earlier, or that proper trials should have actually been done to know the efficacy and safety before testing it on the public?

bhickey
9 replies
5h44m

Either would've been preferable to what was done. Waiting on a provably fruitless trial in the midst of pandemic is regulatory homicide.

Throughout 2020, more than 9% of all people in nursing homes died of covid. Depending on age case fatality rates were upwards of 50%. The vaccine should've been offered to these people on a compassionate use basis. Even at the time it was obvious that actual harm posed by the virus vastly outweighed any hypothetical risk of adverse vaccine reaction. Drastically expanding the vaccinated population through compassionate use would have rapidly provided efficacy and safety data.

_heimdall
4 replies
5h36m

Throughout 2020, more than 9% of all people in nursing homes died of covid. Depending on age case fatality rates were upwards of 50%.

That's just about most difficult population to determine primary cause of death for. Most people in nursing homes have multiple comorbidities and a long list of medications. Its easy enough to know when someone died with Covid, its much more difficult (if not impossible) to know after the fact whether that's what caused their death or if the infection began after an existing condition worsened and weakened their immune system further.

Drastically expanding the vaccinated population through compassionate use would have rapidly provided efficacy and safety data.

That wouldn't have helped get efficacy or safety data for the general public though. Vaccinating that population could absolutely have helped determine efficacy for that population and I agree it feels like a reasonable action given the potential risks for that population, but the data wouldn't be useful for the general public that are younger and/or in better health prior to infection.

bhickey
3 replies
5h18m

That's just about most difficult population to determine primary cause of death for.

Nursing home quality, COVID-19 deaths, and excess mortality https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776351/

At the peak, excess nursing home mortality was nearly 6000 per week. Quibbling about "died with covid" versus "died of covid" isn't a useful exercise. Dead is dead and the excess mortality came from somewhere.

_heimdall
1 replies
5h7m

Quibbling about "died with covid" versus "died of covid" isn't a useful exercise.

It isn't quibbling when the specific topic is whether or not to treat a population with an untested vaccine (assuming the trials were skipped for at risk populations as proposed above).

In a general sense, I totally agree the "with" versus "of" debate isn't useful. But when considering giving an at risk population an untested vaccine, how is that not important? Any intervention could have downsides, and more importantly an preventative intervention for a secondary infection may not be worth the risk depending on the risk profiles.

One tricky question that would have to be answered is whether the excess deaths were related to changes in nursing home treatment and general conditions. Nursing homes were effectively locked down in many areas, reducing human contact and potentially negatively impacting care. Vaccines would have no impact there, and if the untested vaccine has negative side effects we would have only made things worse.

wbl
0 replies
10m

Vaccine risks tend to be very quickly detectable. The phase three trial timing was driven by needing enough infections and there weren't enough.

linuxftw
0 replies
3h52m

People in nursing homes died from untreated illness. They were completely locked down, and isolated from friends and family. They weren't allowed to be transported to actual hospitals. Anyone with simple bacterial pneumonia was left to die.

In the UK, nursing homes were discovered to be sedating patients and not administering water and nutrition. I wouldn't be surprised to learn the same happened in the US.

pfisch
3 replies
4h20m

If something would've gone wrong with rushing the vaccine like that it would've given the anti-vax people a massive boost and the vaccine refusal rates would've skyrocketed.

The refusal rates were already too high with anti-vax people making up lies/distorting data. If they actually had real data things would've been much worse.

someuser2345
0 replies
3h48m

Something did go wrong; of the 3 vaccines the FDA approved, 1 of them had to be recalled due to causing fatal blood clots.

_heimdall
0 replies
3h31m

How do we define an acceptable refusal rate? The vaccines were largely untested and given under emergency use authorization. Shouldn't it be reasonable for people to choose for themselves whether to take part in the vaccine campaign or not, especially when we can't provide solid data to support safety or efficacy?

At the end of the day, in my opinion, there is no magic number for vaccine acceptance that is a metric to define beforehand. Refusal rates are a backward looking metric only and simply reflect the willingness to participate and trust in the general public.

AnimalMuppet
0 replies
2h38m

How about telling the public the truth? Say something like, "This particular vaccine has not been tested up to normal FDA standards. It may not be as safe as other vaccines. But we are convinced that it will do more good than harm, given the danger of Covid for the unvaccinated."

You could let the public make an actual decision based on actual information, rather than telling them little, projecting false certainty, and then trying to force them to do what you think is the best course. I mean, look, not everyone can be treated like adults. But I think the majority of people can. Tell them the truth, and let them decide.

refurb
0 replies
4h55m

Still, the FDA approved it.

The FDA approved it via accelerated approval. The intent being "allow access to promising medicine while additional data is collected".

zoobab
0 replies
6h35m

"The FDA (and EMA in Europe) are the only thing that protects desperate patients from fraudsters, charlatans and pharma-companies just looking for a return on their investment."

EMA has some people that were recruited from Big Pharma.

wbl
0 replies
11m

Remember the pandemic? The FDA had safety and effectiveness data by end of August for the vaccine and were unprepared to do an analysis in less than a few months. Nor did they consider drafting the party boys of the Ozarks to get the efficiency data faster. As a result the winter of 2020-2021 saw thousands of preventable deaths.

There's also the part where distribution was done in a way that deliberately killed people so that racial equality goals could be met. Perhaps the worst example of this kind of thinking were teachers in SF getting vaccinated but school not starting again.

ndr
2 replies
10h39m

True for _all_ 'safety stuff.' However, safety requirements for late-stage patients with very few other options ought to differ from safety requirements for mass adoption.

vkou
0 replies
9h31m

They already do.

rl3
0 replies
10h17m

However, safety requirements for late-stage patients with very few other options ought to differ from safety requirements for mass adoption.

Do they not already?

advael
2 replies
10h35m

I mean, if you have an aggressively terminal disease with no known cure, I think the risk-reward calculus is somewhat different from the average drug

The issue, as comes up incessantly in all manner of situations, is the way we regulate drugs as a whole. A lack of safety testing should mean a higher standard of informed consent should be used, not that it should be illegal for someone to get ahold of it

I see lots of benefit to regulatory agencies controlling what claims can be made about medications and holding people selling them to account for quality control failures. Agencies preventing consenting adults from making their own risk-reward calculations does badly on both principle and outcomes

scott_w
1 replies
8h0m

While I agree that my calculation on safety would be different for a terminal illness for which no cure exists, we still need to be careful. The very nature of this situation creates desperate people who are willing to ignore a simple warning label in favour of hope.

Any system / regulator still needs to force companies to prove their treatment has the claimed effect, and block any that simply don't. On safety, I think there's more wiggle room, however. Treatment here can be based on likely ill effects vs the known effects of the illness of the patient.

advael
0 replies
3h23m

Nah, I actually think the effectiveness standard is far worse than the safety standard due to what a "block" means and how "effectiveness" is tested.

An RCT, the gold standard by which medicines are often tested, can easily show a negligible effect size because of the vast confound space of individual differences. A medicine that works perfectly for many of a study's participants will be considered "ineffective" routinely

And hey, in cases like that I think the regulators should absolutely have the power to say "selling this without explaining these caveats is criminal fraud", but not that people can't try the drug anyway if informed of the risks and low likelihood of success as determined by the agency's analysis

In an effort to standardize process and appease large incumbent industry players (often, as here, by erecting enormous entry barriers in front of lucrative markets), we frequently create metrics that are too blunt and remedies that favor governments flexing disproportionate power over the lives and choices of individuals

okaram
0 replies
3h22m

Yes, the system works, and we have very little poison being sold as medicine.

The issue is that with some illnesses/stages, we do not have a good treatment, and a lot of people would like the calculus to be different. We do have compassionate drug rules, but they're a pain for many people.

I'm not in that situation, and not sure how I'd react; but I can see how, having an incurable illness, with tons of suffering or a few months left to live, I might want to try everything. Hydroxychloroquine, Chinese acupuncture, herbal remedies, and experimental treatments.

emblaegh
0 replies
10h39m

You seem to imply that the only possible source of slowness if safety, which might not be the case (I've no idea).

ben_w
0 replies
8h17m

What do you mean by slowness? They can't skip all the safety stuff!

One can be fast and safe, it's just that requires spending a lot of money.

It's analogous to cache prefetching and branch prediction in CPUs, except the cost of bad predictions is measured in millions of dollars rather than tens of CPU cycles, and also that the predictions are much harder.

briffle
0 replies
3h38m

Not that it should matter, but they are also VERY expensive. There is a new standard for NCPDP (how pharmacies and payers send transactions for payment) coming out in the next few years called F6. One of the big changes over the current standard is drugs that cost more than $1M can be processed in a single transaction. https://www.cms.gov/files/document/fact-sheet-11-2022.pdf

ekianjo
21 replies
16h2m

but the canine patients lived a median of 139 days, compared with a median survival of 30–60 days typical for dogs with the condition

so you might get an improvement in overall survival but not a cure for GBM

notdonspaulding
8 replies
15h45m

GBM median survival for humans (according to the article) is 15 months.

If the effect is linear, the boost to survival time in humans would be an additional 19 months. With the death sentence of GBM hanging over your future, an additional year-and-a-half is huge.

SoftTalker
7 replies
15h32m

It is and it isn't. A year and a half would go by so quickly. But if it were a high-quality year and a half and not spent in a hospital ward, I guess it's better than the alternative.

magicalhippo
1 replies
10h43m

It's highly non-linear, as you allude to.

For a mother with a young child, getting another 1.5 years can be the difference between the child not knowing their mother and having some memory of her.

For someone with no or adult children, it can be a lot less significant. My dad passed away from cancer when I was 30 and while I certainly would have taken an extra year with him, it wouldn't have changed much.

CalRobert
0 replies
8h50m

Nothing like a deadline to make the most of 18 months. I have a 4 and 6 year old and if I were in this situation I'd cherish the hell out of that time. And hope for further improvements in treatment (and a stroke of luck) in the meantime.

afavour
1 replies
14h50m

How about we could let people make that decision for themselves?

SoftTalker
0 replies
14h37m

I said nothing about making the decision for anyone else.

panosfilianos
0 replies
7h19m

You could say the same for 20 years, in the grand scheme of things.

notdonspaulding
0 replies
5h19m

It is and it is. My dad died of a GBM in 2022, 17 months after his diagnosis. If he had had another 19 months, I'd have made him breakfast this morning.

I find it much easier to sympathize with people's desire for additional time with terminally-ill loved ones now.

agumonkey
0 replies
6h47m

I'm in the camp of having 18months of non painful survival being a massive change, because it buys you time to wait for another therapy later.

mlyle
6 replies
14h27m

Very unlikely to be a cure for GBM, but there's often the hope that therapies can stack very well-- both from combined effect against disease and sometimes sensitizing the disease to other therapy. The dogs were not receiving the human standard of care treatment-- who knows what surgery, radiotherapy, immunotherapy, and chemotherapy can do combined.

s1artibartfast
5 replies
13h48m

The dogs were not humans with human cancer, so we shouldn't expect a clean translation of the results

mlyle
4 replies
13h7m

Of course not, and the relevant xkcd, etc. Not our first rodeo here. It's going to take a long time to get gold standard proof that survival is augmented.

It's still exciting news. They're ramping up through phase 1 to phase 2 in humans, and already have evidence of similar immune response in human patients.

ekianjo
3 replies
13h4m

this requires individualized treatment based on the description which will make the implementation costly and impractical. They need to extract a piece of the tumor from the brain.

mlyle
2 replies
12h47m

Surgical resection of glioblastoma is usually (not always) one of the first steps in treatment, so you get that "for free".

But yes, I would expect it to be quite costly.

ekianjo
1 replies
10h0m

yes but thats only the first step in this case. then they need to prepare the individualized mRNA shot from there. How long it takes and how complex it is is another question.

mlyle
0 replies
4h19m

Yes, most of the promise of mRNA with cancer is the prospect for individualized therapy. But individualized therapy intrinsically means you're going to be a doing a patient-specific manufacturing step.

Sequencing and RNA synthesizing are widely available commercial services at this point, though not cheap.

There's a lot of magic to take mRNA and formulate it to last in the human body and go and do what you want, but it isn't likely to be the costly part of all of this if there's some small volume of people being treated this way.

adamredwoods
2 replies
15h50m

If any treatment can extend the life of a patient up to 3 times (as was in the canines), that's significant. Some treatments only have a response efficacy of a few months, but you add a few of these together in sequence, and you build a year.

ekianjo
1 replies
15h2m

still does not change my conclusion. its a treatment, not a cure.

iancmceachern
0 replies
14h56m

Yet

jmward01
0 replies
15h50m

I'm a bit more optimistic. The article specifically mentions that it is too soon to look at efficacy. There could have been a lot going on with these dogs that shortened their lives that was unrelated to the GBM. Optimizing the treatment for dosing, timing, etc and applying it sooner are likely to greatly improve its efficacy.

chefandy
0 replies
14h33m

Indeed, you have ascertained the the article's topic— big progress in GBM research— and correctly distinguished it from a topic the article wasn't about.

dbbk
5 replies
7h34m

How can it be a vaccine if he already had Glioblastoma? Surely it's a treatment not a vaccine?

andreasmetsala
1 replies
7h20m

A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease.

With viruses and bacteria the immune system eventually catches up and vaccinating tends to be done before the host is infected (rabies vaccination is an outlier since it still works even after infection during the latent period). With cancer the immune system usually doesn’t recognize the threat which is why vaccinating after the fact is still effective.

Salgat
0 replies
2h24m

Yep, the goal of these vaccines are to program the body to have a strong immune reaction to the cancer/tumor.

muldvarp
0 replies
7h24m

Not all vaccines are (purely) prophylactic. This is what we would call a therapeutic vaccine.

adrianmonk
0 replies
2h37m

The definition is broader than that. Think of a vaccine as something which teaches your immune system to fight some particular thing.

The most common application is as a preventative measure to protect you from an infectious disease. But it can be used for other diseases (like cancer, which is not infectious) and it can be used after you're sick.

Fun fact: if an unvaccinated person is exposed to measles, they can get the MMR within 72 hours of exposure, and it will still reduce the severity of the disease. (Source: https://www.cdc.gov/vaccines/vpd/mmr/public/index.html )

GenerocUsername
0 replies
2h39m

The definition of vaccine was changed during the covid vaccine rollout. The new definition is more expensive than the traditional description.

DoesntMatter22
3 replies
9h5m

ThTs pretty good because glioblastomas are real real bad

joak
2 replies
7h59m

A friend of mine 23 years died of glioblastoma. Completely undetected, he went to bed with a mild headache and died during his sleep.

If we find a cure for glioblastoma the challenge would be detection before it's too late.

shitter
0 replies
2h27m

And they tell me my health anxiety is "irrational".

DoesntMatter22
0 replies
1h29m

To be honest that's not a bad way to go out. Better than years and years of treatment for something and a slow death. But yeah, the detection aspect would be interesting assuming these mRna viruses could cure cancer.

amelius
2 replies
8h13m

So now we only need to detect the cancer in an earlier stage, and surgery might not even be necessary (?)

AdmiralAsshat
1 replies
3h21m

Even if the immune system completely destroys the tumor, I'd be worried about tumor detritus (is that the right word?) floating around in the brain? It might be better than the alternative, but I'd think that's one spot you really don't want cobwebs gathering in.

rpmisms
0 replies
3h11m

If the immune system actually works properly, no, not really a huge concern. Leukocytes and macrophages fully consume foreign matter, enclosing it in a phagosome. This then merges with a lysosome, where the matter is broken down into harmless components, although some stays on the surface of the cell to activate other immune cells against that particular brand of gunk.

AlanYx
1 replies
4h10m

Is this the same as glioblastoma multiforme (GBM)? I'm not a doctor, but I thought GBM was a death sentence? Progress on that front would be amazing.

ska
0 replies
4h1m

Yes, it’s that cancer. Median survival is a little over a year iirc.

Often treatment focus is on quality of life issues, because they are often found due to physical deficits.

stainablesteel
0 replies
1h25m

they couple it with surgery despite how the vaccines are supposed to remove the tumors themselves?

it seems odd but i guess its meant to aid the process?

freefolks
0 replies
3h16m

My father went under surgery to get this removed. It was 6cm and completely grew back within 3 months. He died 7 months later.

willis936
14 replies
16h11m

My SO's PI died of Glioblastoma a few years ago, completely derailing their career path, halting all research, and leaving behind a grieving and struggling family. It's difficult to picture how my life would be different had this treatment been available.

jeffbee
10 replies
15h57m

completely derailing their career path, halting all research

That's a real odd way to characterize a person's death.

AnarchismIsCool
8 replies
15h56m

Read the sentence again, more slowly this time.

noncoml
3 replies
15h47m

PI = ?

SoftTalker
1 replies
15h34m

Probably Principal Investigator. I'd guess the "SO" is a PhD student and now his/her program is up in the air.

echelon
0 replies
15h11m

Significant Other.

bglazer
0 replies
15h39m

Principal investigator. It’s what phd students call their academic advisor/boss during graduate school

ianbutler
3 replies
15h52m

It’s still odd to characterize a person’s death in terms of someone else’s career progression. Probably because it’s uncommon to see a death characterized by it’s second order effects. Usually it’s the family or friends and it’s more personal. OP didn’t say anything wrong though.

arcticfox
2 replies
14h35m

It’s still odd to characterize a person’s death in terms of someone else’s career progression.

OP even went another level, since it was their SO's career progression that was affected, thus affecting OP. Agreed, they're not wrong, but it was odd.

4death4
1 replies
14h25m

They’re not wrong in the sense they’re factually correct: OP’s life would have been different had a cure been available. But if OP’s SO approached her PI on their deathbed and said “Dear PI, what about my SO?” They’d probably be met with incredulity.

CookieCrisp
0 replies
10h36m

Well it is a good thing that nothing like that happened then, isn’t it?

dotnet00
0 replies
13h48m

I don't think they meant it in a negative way. The last line makes me think they mean it in a sort of self-reflective butterfly effect way.

Similar to how anyone might reflect on how the death of a relative or friend ultimately led them to being the person they are now in some way.

eps
1 replies
10h23m

What's "PI"?

mkoryak
0 replies
15h24m

My dad died from that also, luckily for me, I was still in middle school and it had almost no impact on my career path. It's difficult to picture how my life would be different had this treatment been available.

jmward01
13 replies
16h46m

When COVID hit one of the few positives was that a lot of people joined in cross-discipline research to address it. This type of treatment sounds amazing, and I know mRNA vaccines were in development for a long time before COVID, but I have to wonder if this research would have taken a lot longer to happen had COVID not happened. What other secondary impacts has the research into COVID had?

zer00eyz
10 replies
12h12m

MRNA's for aggressive cancers are going to do some amazing things. This is one example of "death sentence" cancer being stopped cold. To that end, the trade offs for MRNA's make complete sense. It's a great place to do long terms studies and see what happens down stream.

What covid did prove out is that there IS risk. https://www.health.gov.au/our-work/covid-19-vaccines/advice-...

Biologics (what vaccines are) are weird. The FDA should be stepping back from restricting the use of these on INFORMED patients who have limited other choices and mandating the long term study that we need for this class of treatments. IF were extending peoples lives and finding those secondary a tertiary risks in patents who would have otherwise died we will all benefit in the long run.

Between Pro and Anti vax camps it is dam near impossible to have a rational conversation about the topic. One more thing that has been polarized into the abyss... sigh!

soco
7 replies
10h5m

We had a nice discussion here, you had your arguments, got the few mistakes pointed out, all factual, civilized and nice. Nobody called you sheep, antiamerican, or puppet of the global government. So let's not bring the anti-vax "polarization" into this, because the two camps are simply not the same. Edit: I have yet to see such a rational discussion with an anti-vax. Won't say it cannot happen, but to me it's like bigfoot.

happens
6 replies
9h55m

If the were able to have that kind of discussion with you on the pros and cons of vaccines, would you still perceive them as antivax?

soco
5 replies
9h37m

Interesting point! Anti vaccines yes obviously, but I wouldn't call them "antivax" (anymore) as it seems I reserved in my mind that name for the wild mob - for better or for worse. Because there's no good thing without downsides and discussing downsides is just as important, regardless how one prioritizes them. We are all different organisms and what works for one won't necessarily work the same for the other, and we need solutions for all.

mewpmewp2
4 replies
8h3m

Thing is that people used to label you as anti vax during that time period even when you thought vaccines as a whole were a good thing, but in certain situations they did more damage and in other situations it was possible that risks vs benefits calculation wasn't clear.

jijijijij
3 replies
5h16m

That's because the anti-vax people are sometimes an actual threat to other people's lives.

Especially during the pandemic every argument was had ad nauseam and a (similarity to) certain narrative wasn't perceived as coming from good faith anymore. People were tired of explaining the difference between DNA and RNA, between relative risks of the vaccines and infection, herd immunity, ... . At some point you never knew, if the person you are debating will go full conspiracy nut. Even genuinely skeptical people were often worried because of opportunistic clout chasers were spreading misinformation.

See the comment above where the AstraZeneca vaccine got conflated with mRNA vaccines. Bad start...

There were no vaccination mandates. However, "anti-vaxxers" were offended people decided to keep them out of their groups, shops, communities, ... by vaccination status. They want to have the cake and eat it too. Their idea of discrimination is overreaching and entitled.

Izkata
2 replies
5h6m

There were no vaccination mandates.

"Get the vaccine or lose your job" absolutely is a mandate. This really was a thing.

jijijijij
1 replies
3h30m

A private de facto "mandate", not a governmental one.

Well, yes, that's what I was getting at: Freedom cuts both ways here. If you choose to not get vaccinated, others should be allowed to, at the very least, choose not to have you around. Immunity is not a private belief, but has severe, sometimes existential implications for other people.

I assume, it's pretty much the same with guns in the US. You are allowed to own them, carry them, but not allowed to bring them everywhere, if someone's ruling within private jurisdiction forbids it.

Izkata
0 replies
3h8m

not a governmental one.

Only because it was struck down by courts. The US government did attempt it, and even told employers to abide by it while they appealed (before it was struck down again).

jijijijij
0 replies
10h50m

The AstraZeneca vaccine mentioned in your link is not mRNA based.

defrost
0 replies
10h46m

What covid did prove out is that there IS risk.

Not an mRNA vaccine and vaccine risk regardless of vaccine type was known and acknowledged for many decades before COVID.

andreasmetsala
0 replies
6h56m

This type of treatment sounds amazing, and I know mRNA vaccines were in development for a long time before COVID, but I have to wonder if this research would have taken a lot longer to happen had COVID not happened.

At least BioNTech was able to take the billions they made from pivoting into COVID vaccines and use the money to speed up their cancer-related pipelines. Running clinical studies is expensive and difficult to do if you have to beg for money for an unproven platform.

Terr_
0 replies
16h40m

That reminds me of a piece about the "source code" of one of the mRNA vaccines [0], which had an amusing bit showcasing how one kind of pre-pandemic research was hugely important in preparing the necessary tools for when they were needed:

It turns out that, unmodified, freestanding Spike proteins collapse into a different structure. If injected as a vaccine, this would indeed cause our bodies to develop immunity... but only against the collapsed spike protein.

And the real SARS-CoV-2 shows up with the spiky Spike. The vaccine would not work very well in that case.

So what to do? In 2017 it was described how putting a double Proline substitution in just the right place would make the SARS-CoV-1 and MERS S proteins take up their ‘pre-fusion’ configuration, even without being part of the whole virus. This works because Proline is a very rigid amino acid. It acts as a kind of splint, stabilising the protein in the state we need to show to the immune system.

The people that discovered this should be walking around high-fiving themselves incessantly. Unbearable amounts of smugness should be emanating from them. And it would all be well deserved.

[0] https://berthub.eu/articles/posts/reverse-engineering-source...

TheCleric
9 replies
4h38m

As we see more and more promising therapies like this, that are essentially custom fit to the patient, it makes me all the more worried about the US health care systems. A treatment like this will be expensive, which in the long run means that we'll have a society where people with money won't have cancer (or at least will have a less deadly version), while the people without money will not. We'll be converting cancer to a problem of poverty. None of this is to say that we shouldn't pursue these advancements, but rather we should start thinking about how we can change our system to ensure that every member of our society has equal access to medicine.

s1artibartfast
4 replies
4h25m

we should start thinking about how we can change our system to ensure that every member of our society has equal access to medicine.

I dont think that is a healthy or reasonable goal, in the US or anywhere. Some care is labor intensive and costly, and simply not scalable to everyone. It is possible that time helps reduce the burden.

The only way to have equal care is to eliminate high end care.

beezlebroxxxxxx
3 replies
3h54m

The only way to have equal care is to eliminate high end care.

That's one way to think of it. But you also can just say: the only way to have equal care is to raise the standard of all care to the quality of high end care. That's worth trying to achieve even if it's not logically perfect. Most things in life aren't but trying to get there is still a "reasonable goal". It's just about priorities.

The elephant in the room is also access to preventative care. Many people wait until the last possible moment to seek medical care because they can't afford otherwise, or do not have access to local medical facilities. Improving access to preventative medicine and care, which is often cheaper and more simple than cutting-edge procedures, would lower the overall demand on last-minute medical infrastructure, like an ER or hospital, which is often what people think of when someone says "access to medicine". An excellent example of this is Costa Rica, where much more effort is spent on access to preventative medicine and all of the infrastructure required for that. As a result, Costa Rica's health care system rates higher than the US while also spending 1/10th per capita on healthcare.

A lot of the healthcare system in America is just what we've ended up with, often as a result of greed and a relatively recent extreme distrust of public options, rather than some sort of clear eyed logical end point of healthcare rationalization. Improving access to medicine and raising the over standard of universal care is still a goal worth trying to achieve.

snikeris
1 replies
2h3m

That's one way to think of it. But you also can just say: the only way to have equal care is to raise the standard of all care to the quality of high end care. That's worth trying to achieve even if it's not logically perfect. Most things in life aren't but trying to get there is still a "reasonable goal". It's just about priorities.

This is a good example of the common liberal fallacy of Utopianism.

s1artibartfast
0 replies
1h46m

Im not familiar with the concept. Is Utopianism the phenomenon of focusing on an a goal, without considering the cost of achieving it, and critically considering what it would realistically look like when they are achieved.

s1artibartfast
0 replies
3h33m

I agree it makes financial sense to provide universal access to preventative care and basic (read cheap) healthcare.

I think it is counter-productive in addition to being logically irrational to focus on equal access to high end care. It isn't possible and it poisons the well for meaningful change. Not everyone should have access to 10 million dollar care on the social dime. There is no upper limit on possible costs, so actively seeking equality just means banning higher care for those who can afford it.

I dont think that the US outcome is the result of greed. companies are just as greedy in costa rica or eurpoe. Rather, US healthcare costs are the result of illogical and schizophrenic policy choices, with incompatible choices that dont work together. I could rant for hours about what those are, if you are interested. At the end, it is like a crowdsourced car that doesnt work. Someone picked a porche engine, and someone else picked bicycle tires, and someone else picked a tractor frame, so it doesnt work at all.

andsoitis
1 replies
4h31m

We'll be converting cancer to a problem of poverty.

Outcomes are already disparate.

” People in low- and middle-income counties in the United States are more likely to die of cancer than those who live in high-income counties. Eight factors, including lack of access to high-quality clinical care, food insecurity, smoking, and obesity may explain more than 80% of the relationship between poverty and disparities in cancer death rates at the county level, according to a new study.”

And

” In low-income counties, the average cancer death rate in 2014 was 230 per 100,000 people, compared with 205 per 100,000 in middle-income counties and 186 per 100,000 in high-income counties.”

—- https://www.cancer.gov/news-events/cancer-currents-blog/2018...

xattt
0 replies
4h23m

In Canada, despite free healthcare, some of this comes down to how much personal research you do and how hard you advocate in order to be treated at a high-skill facility.

It is still an SES game, because higher levels of education (correlated with income) allows individuals to see beyond “well the doctor told me, so that’s what I’ll do”. Higher SES also comes with the ability for a more flexible work schedule, and the ability to travel to larger city centres where the high-skill care is more likely to be.

martindbp
0 replies
3h23m

Capitalism and technology will make it cheaper over time, if we just let it. Africans without reliable electricity has magic pocket devices straight out of Star Trek. We can find a way to make personalized medicine dirt cheap too, but you can't force it through legislation.

deadbabe
0 replies
4h13m

Cancer being mostly a problem of poverty is still a substantial upgrade from being a problem that just kills all people with little to no mercy.

max_
8 replies
13h37m

Is there a good book about cancer for a layman? That can help them understand what exactly the disease is, it's variants and a list of potential strategies to beat the disease.

otteromkram
1 replies
13h32m

Wikipedia is usually a pretty good starting point. In addition to summarized content, reference links should be available.

max_
0 replies
13h2m

Wikipedia is a rabbit hole. It seems too wide.

I want someone that has already done comprehensive research to guide me on what I should be paying attention to.

liquid_bluing
1 replies
12h17m

I found this book, which traces the surprisingly long and fascinating history of using immunotherapy to treat cancer up to the present day, well, fascinating:

The Breakthrough: Immunotherapy and the Race to Cure Cancer - Wikipedia https://en.wikipedia.org/wiki/The_Breakthrough:_Immunotherap...

My uncle died of a glioblastoma, and shortly after I read this book, I was myself diagnosed with cancer (treated conventionally, hopefully cured). Immunotherapies like mRNA vaccines seem to be our best hope for finding reliable, permanent cures for a lot of different cancers. I am sorry that for many of our loved ones, a cure will have come too late.

rob74
0 replies
8h49m

the surprisingly long and fascinating history of using immunotherapy to treat cancer

Well yeah, it has been known for a long time that cancer can do what it does because of the immune system's failure to eliminate the "defective" cells. Also, there are the rare "spontaneous remissions" where, for some reason, the immune system eventually catches up and manages to destroy the cancer. So there have been many attempts to harness the immune system in cancer treatment. Glad to see that all that work is finally bearing fruit (fingers crossed)...

stenl
0 replies
12h19m

”The Emperor of all Maladies” by Siddhartha Mukherjee is fantastic

Wonnk13
0 replies
7h35m

The Emperor of all Maladies

sharpshadow
2 replies
6h51m

“To generate each vaccine RNA was first extracted from each patient’s own surgically removed tumor…”

Wait!? It can be any tumor right or do they have to open my skull and take a sample of the actual tumor they want to get rid of.

jncfhnb
0 replies
6h19m

It has to be the same tumor

gizmondo
0 replies
3h57m

I guess you can wait for metastasis instead for easier access. /s

MisterDizzy
2 replies
1h54m

After my COVID shot, I got 2 or 3 days of Transient Global Amnesia. It has scarred my son, who worries about amnesia every single time he's a little delirious from an illness or some such.

By my estimation, the people who threatened and socially pressured others to get an unfinished, experimental gene therapy injection that was always socially enforced to be referred to in polite company as a "vaccine" are the ones liable for any damages that might occur. My son may be scared of random amnesia for the rest of his life. What does he get? What do I get?

What do the people get who believed themselves to be above moral reproach specifically because they were afraid? How do we make sure such people never get to make a decision on my or my sons' behalf ever again?

To say nothing of my cousin, a death of despair due to overblown lockdowns that did more damage than COVID.

What do we do to make sure this doesn't happen again? The answer cannot be "nothing."

tjarrett
0 replies
1h31m

Wow that sounds pretty scary. I'm sorry you and your family had to endure that. I'm also very sorry about your cousin.

I share some of your concerns about using mRNA technology as an annual preventative solution against COVID and flu. Even though I'm triple Pfizer mRNA vaccinated I'd probably go for a non-mRNA solution going forward (my employer finally dropped their COVID vaccine requirement but maintain an annual flu vaccine requirement).

But it seems to me that mRNA is a fantastic tool for fighting deadly cancers. Without treatment, the patient is absolutely going to die.

I know. My mom died of glioblastoma back in September 2019. The tumor was wrapped around her thalamus so we had very limited treatment options -- at the time the most advanced treatments needed access to the tumor which is hard to do when it's in the center of your brain.

Hang in there MisterDizzy and, since we are on Hacker News here, remember one of the principles of software development -- use the right tool for the right job. For me, right now, that looks like tried and true protein-based vaccines for those annual vaccinations and fancy mRNA platforms for those specialized treatments.

Sammi
0 replies
1h40m

The article isn't about that vaccine.

monkburger
1 replies
11h57m

mRNA research is going to change medicine for the better.

_heimdall
0 replies
6h29m

It has that potential for sure, but I hope the people researching and developing these tools aren't that optimistic. We need to be skeptical until treatments are proven, going in optimistic for a field-changing breakthrough is a great way to misread the data or fail to design proper studies.

MisterDizzy
1 replies
2h17m

I'm confused and the term vaccine. My understanding was that a vaccine contains a deactivated virus. Is mRNA not a form of gene therapy? I understand not wanting to spook people away getting the shot during an actual pandemic and altering terminology, but isn't this something other than a "vaccine"?

Sammi
0 replies
1h33m

"A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease.[1][2] The safety and effectiveness of vaccines has been widely studied and verified.[3][4] A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and recognize further and destroy any of the microorganisms associated with that agent that it may encounter in the future."

https://en.m.wikipedia.org/wiki/Vaccine

Sounds like this is a vaccine given that criteria.

uyzstvqs
0 replies
10h4m

This is an area where mRNA immunization can be very effective. I hope that this can be widely deployed in the next years, it can make a real difference. Something that also has great potential is the use of phages, that should definitely receive at least equal parallel research attention.

pfdietz
0 replies
5h23m

I'm glad they're testing this. A vaccine approach always has the risk of hitting healthy tissue as well with the immune response. And when that tissue is brain tissue...

Testing is necessary anyway to get insurance companies to pay for something. They like to deny coverage, and if the treatment is not proved to work that's an easy excuse.

mlyle
0 replies
14h27m

GBM is horrible.

At my first company, our VP of Sales, Luke Little, was one of my favorite people to hang with; I was still barely 20 and he was in his 40's but he had quite the mischievous twinkle in his eye and was willing to join us kids in tomfoolery and tell us about the world. We were acquired and got a great exit in July; he had a seizure driving the Cobra he bought to celebrate a few months later; he went downhill quickly and died within a couple of years. He had a young son, too.

howbadisthat
0 replies
11h48m

Cancer tends to have an interesting relationship with cellular protein transport. And as a consequence has problems dealing with heat. The protein transport mechanism by which immune surveillance is conducted is shared with cells surviving heat increases via ejection of heat shock proteins.

I once tried to find if there were any studies about incidence of cancer plotted against incidence of high fever in the same individuals but wasn't able to find anything. It may also point to the incidence of cancer actually rising due to suppression of other diseases.

This is plausible due the fact that diseases are a constant in nature and therefore evolution would take their presence as a given as much as the seasons or the sun. It would be very unfortunate if numerous anti-cancer adaptions simply haven't evolved because regular fevers took care of those cancer precursors.

adamredwoods
0 replies
15h47m

Sounds effective, I've always had a hunch the real path to controlling cancer is not a singular approach. Cancer mutates too much.

> “Instead of us injecting single particles, we’re injecting clusters of particles that are wrapping around each other like onions, like a bag full of onions,” said Elias Sayour, MD, PhD, a UF Health pediatric oncologist who pioneered the new vaccine. “And the reason we’ve done that in the context of cancer is these clusters alert the immune system in a much more profound way than single particles would.” Results from the canine trial showed how the vaccine reprogrammed the tumor microenvironment (TME) within days, allowing the activated immune system cells to fight the tumor.

https://www.cell.com/cell/abstract/S0092-8674(24)00398-2

MisterDizzy
0 replies
2h21m

This seems to be a much better application of a gene therapy shot of this kind that has such a small targeted scope. A virus that mutates would clearly be an exercise in playing constant catch-up, but this seems a lot more realistic.

Is there anything that works to replace the delivery system that's more reliable/predictable than the lipid-based carriers?