If this turns out to work as promised, in a idealistic universe, Moderna gets a big influx of money from all countries in the world and they immediately publish details and surrender any patent allowing the treatment to be produced worldwide and be affordable for everyone.
Past mRNA cancer vaccines haven't failed to get through trials because of ineffectiveness. They failed clinical trials in the 2000s and 2010s due to their side effects being too bad. The side effects of mRNA vaccines are getting less and less severe over the years, but the proof of the pudding will come in phase III for this vaccine, as with all the other ones.
The side effects of most cancer treatments are aweful. How do they compare?
Most of them are awful but only in rare cases do they cause permanent damage beyond what is already happening with the cancer and usually the patient can recover after the treatment is stopped.
Anything that stimulates the immune system runs the risk of increasing its sensitivity too much till it attacks normal cells and at that point, a lot of horrible things can happen ranging from a new mild allergy to neurological disorders like multiple sclerosis to acute organ failure.
Since the point of the therapy is to get immune cells to attack the cancer cells, there's the very real risk of instead targeting the tissue the cancer evolved from.
Most of them are awful but only in rare cases do they cause permanent damage beyond what is already happening with the cancer
That's simply not true. Chemotherapy, in particular, is ridiculously bad.
Chemo brain is a thing. Another example, people have to wear cold packs on their hands and feet in order to minimize the neuropathy that some chemotherapies can cause. Other chemotherapies cause your veins to leak with attendant swelling everywhere. Several years after therapy, some of that swelling still persists. Radiation is horrendously bad at damaging intestinal tissue. etc.
Yes, it beats being dead. That's about all you can say about it.
I agree. I have not been through it, myself (crosses self), but I live on Long Island, which means that I have watched a lot of people go through it.
Most recover nearly completely, but they all suffer some permanent effects, like sun sensitivity, hair loss, digestive problems, anemia, weakened immune system, etc.
Why would living on long island mean you would watch a lot of people go through it? Is there some some kind of cancer hot spot on long island? Genuinely curious.
Oh, it’s very bad, hereabouts.
Long Island is known as a breast cancer hotspot (especially Nassau County), but I have seen many different types.
I moved here, when I was 28. Before coming here, I had never met anyone that had cancer.
Since moving here, I have known at least one person, every year, that has been battling cancer. This year, it has been 3 fairly close acquaintances.
They keep a lid on it, but it’s bad enough, that it’s pretty much an open secret.
Any guesses as to what's so special about Long Island? I assumed the issue was going to be skin cancer from sun exposure, not breast cancer.
Military base areas have significantly higher cancer rates.
Long Island has historically had quite terrible air quality, as well, no?
Not the best, but the City has worse.
What Long Island is, is the site of some of the oldest heavy industry, built for the world wars.
Many those planes and tanks you see in the documentaries, were often built right here.
And they set it up quickly, with very little regulation. People have been straight-up dumping toxic sludge for decades. Since Long Island gets almost all its water from local aquifers, there you have it.
Traditionally, this kind of thing happens to disadvantaged communities, without much clout, but Long Island has a lot of billionaires (old-money billionaires). They get cancer, as well.
But they are also absolutely aghast at the prospect of government intervention, and hate regulations. Add a bit of mob spice, and you have a situation, where no one wants to raise a stink.
We do have some damn good cancer hospitals, though. Very few of the people I have seen fight cancer have actually died.
Aquifers. Also, it's probably Superfund Central.
A few times a month, I pass a fancy adult condo development, built upon the land that was formerly Deutsch Relays[0]; an old superfund site.
[0] https://cumulis.epa.gov/supercpad/CurSites/csitinfo.cfm?id=0...
failed clinical trials in the 2000s and 2010s
We didn’t start testing neoantigen mRNA cancer vaccines until 2017 [1].
IIRC from when Moderna started getting hot back in 2012 the preclinical trials weren’t going well. I think those were running ca. 2004–2005. Moderna took the infectious disease approach.
This is an oversimplification, but:
Moderna mostly took an initial infectious disease approach because extant mRNA formulations at the time provoked too much of an immune response that neutralized the effectiveness of subsequent dosing. There's a goldilocks amount of immune response you want-- too little and the immune system doesn't learn the antigens you'd like, but too much makes it miss the mark and focus too much on the formulation of the vaccine itself.
For a cancer vaccine that you want to dose multiple times (9 times in this study) to keep up peak immune response this is a problem. For infectious disease, where some early sensitization of the immune system can be enough, it's not so bad.
huh that sounds exactly like machine learning overfitting vs generalization
Well, over-fitting is a term borrowed from biology (and generalisation from economics), so not surprising in grand terms.
Maybe the real surprise for some is that not everything was invented in the valley.
that's definitely not what I meant or implied; it makes sense that the immune system is a classifier of sorts
Interesting analogy and it may not be wrong.
The acquired immune system basically includes a feature where it can squirrel away some of the white blood cells that fought an infection in the past at the site of the infection. This is a subset of the cells that were activated by the chemicals that were found during the infection.
But the immune system doesn't have a great way to distinguish the chemicals that actually cause illness from ancillary chemicals that may have been present during the infection as well. This is one of the root causes of allergies... you get sick with, say, rhinovirus at the same time that the pollen count is really high and your immune system defeats the rhinovirus but squirrels away both the white blood cells that were activated by the rhinovirus and the ones that were activated by the basically harmless chemicals on the surface of pollen grains. Then the next time allergy season comes around, your nasal passages and lungs fill up with pollen grains and the white blood cells close to the surface that were squirled away due to that old rhinovirus infection activate and trigger your immune system to respond to the pollen.
What kind of side effects?
I think you might be confusing mRNA vaccines with immunological cancer treatments in general, which have been tried in trials for decades and have occasionally caused horrible side effects in some patients.
Do you have any references?
Should this really be called a “vaccine”? I feel like that is going to give people the wrong impression about what it does. I think labelling it gene therapy, immune therapy, or something like that would be closer to what it actually does.
Also really interested to see if people will need and/or benefit from periodic re-treatment. I guess they can figure that part out if it makes it to market.
Yes this should really be called a vaccine. A vaccine is a preparation that stimulates the body's immune response against diseases. For example, a specific vaccine injection (such as a flu shot) can boost the body's own immune system to help protect against a specific disease (such as the year's flu variant).
All previous vaccines were aimed at preventing infectious diseases. None of them are (primarily) indicated for preventing recurrence of a non-infectious disease. Whether it meets the technical definition or not, we can probably agree this is fundamentally different to all other vaccines.
Also, since no other vaccines are custom to each patient, using the term “vaccine” could cause confusion. Do we really want to give people the idea that they can be “vaccinated against melanoma” when the reality is that they can receive a treatment to prevent their specific melanoma, which they have to have already had, from recurring? It seems laden with confusion. Personally, I’ll just call it immunotherapy.
All previous vaccines were aimed at preventing infectious diseases.
This is a common misconception, and that's whythe U.S. CDC is now emphasizing that vaccines can do more to help people.
The most important recent example is the world's widespread rollout of COVID vaccines. These are primarily aimed at better protection against severe illness, hospitalization, and death; these are not primarily aimed at preventing an individual from ever being infected by any COVID variant.
Well that’s just plain revisionist history.
Name another example. The flu vaccine, maybe? But that’s because they don’t know which strains to target.
Both the CDC director at the time and Biden said the vaccine would prevent you from getting COVID.
It’s insane we’re changing the definition of words because the COVID vaccines were kinda crappy and that would be bad politically.
Not that the vaccine discussed here shouldn’t be called one - it absolutely is.
No, covid vaccines were not kind of crappy, just the virus itself evolved so rapidly that the virus had evolved enough even before complete rollout of the vaccines. Yet even then the boosted vaccination was highly effective against the delta variant and still effective against omicron on the level par with flu vaccines. Omicron was just infectious on the level of measles and with very short incubation period giving the immune system very little time to ramp up the immune response.
The idea that marketed vaccines are safe & effective has been well marketed and deeply planted in the minds of the public. It's easier to leverage that familiarity than it is to build awareness and trust for "immunotherapy".
Down voted by those who don't understand marketing, human behavior, read the Heath Brother's "Made to Stick", etc.? Love you HN but you're jumping the shark.
Well, they could at least always say something like “…vaccine, but not like you are thinking. You, like billions of other people, have a misguided and frankly incomplete understanding of the word. …”
Why do you wanna call a thing that stimulates an immune response to an antigen a gene therapy?
It's using the same mechanism as vaccines (exposure to the proteins in question), it's utterly bizarre to conflate it with gene therapy.
It's probably reasonable to call it a vaccine based immunotherapy.
Because it transcribes something from a gene?
That's not what gene therapy means.
In 1986, a meeting at the Institute Of Medicine defined gene therapy as the addition or replacement of a gene in a targeted cell type. In the same year, the FDA announced that it had jurisdiction over approving "gene therapy" without defining the term. The FDA added a very broad definition in 1993 of any treatment that would ‘modify or manipulate the expression of genetic material or to alter the biological properties of living cells’. In 2018 this was narrowed to ‘products that mediate their effects by transcription or translation of transferred genetic material or by specifically altering host (human) genetic sequences’
https://en.wikipedia.org/wiki/Gene_therapy#Classification
mRNA vaccines don't alter the host genome, hence not gene therapy. You could use a broader definition I suppose since (ideally) they lead to the production of certain immune cells; and that would also include all other vaccines.
mRNA vaccines are a gene therapy, and a gene therapy does not mean "must irreversibly change the genome".
Take for instance Moderna's own SEC filing discussing mRNA [1], which summarised the regulatory situation:
"Currently, mRNA is considered a gene therapy product by the FDA. Unlike certain gene therapies that irreversibly alter cell DNA and could act as a source of side effects, mRNA-based medicines are designed to not irreversibly change cell DNA; however, side effects observed in gene therapy could negatively impact the perception of mRNA medicines despite the differences in mechanism.
In addition, because no product in which mRNA is the primary active ingredient has been approved, the regulatory pathway for approval is uncertain. The number and design of the clinical trials and preclinical studies required for the approval of these types of medicines have not been established, may be different from those required for gene therapy products, or may require safety testing like gene therapy products. Moreover, the length of time necessary to complete clinical trials and to submit an application for marketing approval for a final decision by a regulatory authority varies significantly from one pharmaceutical product to the next, and may be difficult to predict."
The industry itself was quite open about mRNA being a gene therapy [2].
At some point there were clearly industry and marketing concerns, and we saw a sharp u-turn into asserting they were vaccines, and additionally that any claim they were gene therapies was the mark of an ignorant rube.
On the marketing front: probably a concern that uninformed memes formed around the "changes your DNA" fears, which at the time were unfounded.
On the regulatory front: I seem to recall some potentially more rigorous regulatory approval if they were considered gene therapies instead of vaccines.
It seems rather clear: they are a gene therapy, and because that adds uncertainty in terms of the regulatory pathways, and consumer acceptance, commercial interests worked hard to recategorise them as a more palatable 'vaccine'.
That the term 'gene therapy' is being redefined to exclude mRNA seems an exercise in commerce rather than science, given the history available to anyone who cares to look.
[1] https://www.sec.gov/Archives/edgar/data/1682852/000168285220...
[2] https://asgct.org/publications/news/november-2020/covid-19-m...
But it doesn't. There's no transcribing going on. mRNA is the *result* of transcribing from DNA. The genes aren't touched.
In normal operation the genes are the master blueprints from which work orders (in the form of mRNA) are generated. The cells use that mRNA to build the requested proteins. The mRNA vaccines are bogus work orders slipped into the production queue and they go nowhere near the DNA.
Yes the word 'vaccine' seems misleading to me as well, as people tend to think of vaccinations as ways to prevent contagious illness. I think immune therapy is a much better term.
It is definitely not a gene therapy.
It primes the immune system to be vigilant for certain patterns. That's a vaccine. It is not altering genes, it's not gene therapy. It is not otherwise boosting the immune system, it's not immune therapy.
The fact that it's target isn't realistically transmissible has no bearing on it's nature. We don't give people rabies vaccine to people to keep them from spreading it, either. In humans the R0 for rabies is exceedingly close to zero in any society that understands what rabies is.
The headline borders on clickbait. The topic is a skin cancer vaccine, not a cancer vaccine.
We have seen how that went during covid, so dont i wouldn't hold your breath on it. The only hope is competition from China and others initiating a race to the bottom.
I mean, it seemed like it worked pretty well with covid. Vaccine was produced very quickly, and in most countries was free.
It was a bit expensive, and it took some time to ramp up production. Still impressive, though.
The problem was that almost everyone who got the vaccine also caught the disease.
Vaccines are not intended to prevent people from getting the disease. Their purpose is to make the body defeat the disease faster while taking less damage.
This claim would come as a great surprise to the FDA, as they approved it soley for prevention of COVID.
No vaccine in existence actually prevents infection. Rather, it primes the immune system so the battle is typically a total rout, the invader losing very quickly and the patient never noticing. That's what they got against Covid/Wuhan and the world actually did achieve herd immunity--against Covid/Wuhan. (The Wuhan strain has been extinct for some time.)
Unfortunately, it turned out to mutate quite rapidly (like the flu) and soon the battles weren't always a rout. It still reduces severity, though, and thus is still used.
That's called preventing Covid. Covid is the disease, not simply an infection.
The problem is that the vast majority of people who got the vaccine did in fact notice very well they've had Covid.
The Wuhan strain wasn't that relevant even before the vaccines were widely available.
Which was predicted and expected all along.
Only if you take really awful studies seriously.
Nobody bothered to test this hypothesis in a proper trial.
We knew it would eventually mutate and reduce the effectiveness of the vaccine. The vaccine remained effective in the time it was developed and for a while afterwards.
And, yes, nobody has tested the severity reduction in a proper trial. It would be expensive, difficult and serve little purpose. What we can observe is that given matched populations the unvaccinated die at a considerably higher rate than the vaccinated. Beware of some bogus "studies" to the opposite--which didn't use matched populations. Those at higher risk are more likely to be vaccinated and a vaccinated high risk individual can easily still be more likely to die than an unvaccinated low risk individual.
If by "free" you mean that taxpayers payed huge amounts of money then sure...
It was like $30 a dose or less. Super cheap. Egad.
Not to mention saved significant hospital costs as people were unwell but not sick enough to require more intensive and expensive treatment.
What is wrong in funding everyone's health through taxes? I paid a lot of them for years, although living a quite healthy life, then one day everything changed, and in just a couple years I had to get covid vaccines, a vertebral stabilization after an accident, then two stents after a heart attack. All for free. So far, my healthcare taxes have been the best possible investment.
It wasn't free, just paid by the government means tax money means money that's now missing for other things in countries like Germany because they still are fixated on the 60% debt ceiling based on an Excel error.
I mean the person i was responding to said "Moderna gets a big influx of money from all countries in the world" - i assume that cash would come from tax revenue. Money doesn't just magically appear.
Not free enough for anticapitalists!
Maybe in 30 years when all the patents have expired.
We don’t know how valuable this tech is. It could be worth trillions. It could be niche. Risk sharing, not cost, is the currency of deal making.
mRNA vaccine production methods are tough, e.g. Moderna’s encapsulation technology. Add to that the personalisation required for these treatments, and we’re still far from economies of scale.
…and were invented with publicly-funded research that they’ve now privatized, resulting in large death tolls from vaccine inequity in poor countries.
IMO they resulted in massive reductions of death across the world. In a world where pharma companies needed to surrender their IP if it was too useful, Moderna wouldn't have gotten funded to pioneer this new and difficult technology, and mRNA vaccines simply wouldn't exist.
Having publicly-funded research doesn't mean you can ignore profit either — the public funding for mRNA was that the initial research was done at UPenn, which receives NIH grants. But large research universities don't exist on public funding alone — they license the patents they hold to companies to develop them, which is a huge part of their revenue. For the mRNA royalties alone, in 2022 UPenn received over $750 million, which exceeded the total of all of UPenn's NIH grants for that year combined. Even in smaller-revenue years like 2020, public funding represents significantly less than half of UPenn's revenue sources. Take away UPenn's ability to monetize their research, and their ability to fund the fundamental research goes down too.
In my view the default isn't that diseases cure themselves. The default is people die. If pushing forward the state of the art of vaccine tech didn't need money in order to be built, what was stopping anyone else from doing it? And if it does need money, well... Then it needs to be well-funded, meaning it needs to show the potential for profit. I don't think charity has proven an excellent model for funding advanced scientific development of this kind.
A long wall of obfuscation and pharmaceutical industry apologetics that can be trivially dismissed by simply pointing at myriad other vaccines that were also publicly-funded, are not constrained by IP, and saved millions of lives.
Your last point is also hysterical because yes, the research needs massive investment, the state provides it, and then allows private companies to run off with it and charge them again for the very thing they made possible in the first place. It’s about as insane and corrupt as could ever be imagined.
I’ll also highlight that Cuba developed a highly effective COVID vaccine as a poor country, under extreme sanctions, and shared hundreds of millions of doses to other poor countries, which further demonstrates what you claim to be untrue.
A research is only the beginning. It usually takes many years and lot of investment to bring a drug to the market. There is also high risk that none of the investment will be recouped. That’s the role that private companies can do well. They don’t just “run off with it”.
ASML, for example, benefits heavily from EUV research done in the US with public fund. Yet you can’t say they ran off with it. They invested heavily, and it took them many years to perfect the technology.
Refer, again, to the example of Cuba’s COVID vaccine.
Check out the list of drugs that Moderna has in the pipeline:
https://www.modernatx.com/research/product-pipeline
Almost all of them are still long way to go before becoming commercial products, if at all. Does it look like they run off with it as you asserted? Or do they have to shoulder the development cost and risk?
One of the drugs is of course their COVID vaccine which is a home run. It’s the potential of such windfall that makes them willing to bet on all of the other drugs in the pipeline.
You cited Cuba’s COVID vaccine. How many other drugs do they have in pipeline? Right, not so many compared to all of the drugs developed by private money. Ask yourself, with regard to their COVID vaccine, how extensive was the testing? can they scale the production? how widely can they distribute the vaccine?
Cuba has a fairly large biomedical sector and export industry, despite being under crushing sanctions. It’s absurd to ask about the scale of their development relative to private industry in the US because it’s impossible for them to even gain access to the same raw materials. But that’s also entirely beside the point because the discussion was about whether we need to allow Moderna to rake in billions off public investment in basic research and IP rentiering in order to make COVID vaccines possible. The example of the Cuban vaccine disproves this, but all the pharma apologists of course prefer to talk circles around this point instead of addressing it.
This is an odd complaint for this circumstance.
Those poor countries didn’t materially fund these vaccines’ development. And production was fundamentally constrained; nations entered into bidding wars to secure them. In the end, geopolitics dictated which vaccines—if any—poor people got. Covid vaccines were distributed through non-market channels.
It’s not at all odd because we learned the disastrous, widespread international consequences, of privatization of HIV/AIDS treatments in the 90s and 2000s. Treatments were developed with publicly-funded research in rich western countries, hoarded for profit at the cost of mass death in the developing world, which led to increased severity of the disease from unchecked spread, which then spread back into the countries that hoarded them. There is nothing more fundamentally stupid than trying to manage global pandemics with nationalism and IP restrictions in a world with interconnected economies and constant international travel.
We saw the same in case with covid too. But, ..., the main issue is that those poor countries have increased their population by many orders of magnitude and this makes large scale support incredibly hard. Imagine if African population was still around 200 million people as it was in 50s instead on 1.5 billion it is today.
It's not a general vaccine , but a tailored one aimed at people being treated for cancers that have a high risk of it coming back. So it's not something that can just be handed out to everyone.
I agree though if a general vaccine is created.
I'm really looking forward to a future where this and heart disease or just merely annoying.
In particular:
And let me guess - there's a massive lobbying effort to be able to patent each of these neoantigens, if they're not already getting patents approved for them?
Edit: Ah yes, why patent specifics when you can patent the umbrella which is akin to covering all bases - https://patents.google.com/patent/US10055540B2/en
Very unlikely, as the majority of those neoantigens are unique to the patient (that's why the vaccine has to be tailored for each of them).
Ah yes, why patent specifics when you can patent the umbrella which is akin to covering all bases - https://patents.google.com/patent/US10055540B2/en
I'm not sure that patent is worth much to be honest. The general approach has been known and published in research circles for the better part of a decade before the patent was filed, and actually training a machine learning system in that way that gives usable predictions is still an open problem afaik.
I imagine an individually customized vaccine would still be expensive even if produced at-cost. Things get cheap when they can be mass produced.
From what they said it doesn't actually need to be individually produced. Rather, there are 34 possible targets, which ones are actually used depends on the patient's cancer. You aim at the targets which the tumor expresses, the others would simply cause side effects for no gain.
Thus, instead of custom manufacture your distribution system is 34 separate compounds, the patient receives whatever combination would be best for their tumor. Probably not viable at the ordinary pharmacy level, but viable at the cancer center level or a compounding pharmacy.
Many dedicated pharmacies (not pharmacy sections in stores) have the necessary equipment for compound medication production.
aka compounding pharmacies.
i love this idea. worldbank or imf or gates or thiel foundation compensates the company for opening the patent for the benefit of humanity.
What incentive do Gates or Thiel have for doing that?
I could see Gates doing it.
imagine the conspiracy theories though...
"No you can't just fight cancer this way, that's cheating, drink this completely natural juice made from pulped fruits and vegetables that have been growing separately for 80 million years."
Free market would automatically cause a big influx of money.
A "big influx of money from all countries in the world" - if from governments themselves and not individual citizens buying - would in fact be a proof point against its claimed effectiveness, if forcing the otherwise free market (via easily-commonly captured political-government-institutional channels) is what's required to drive funding towards it, e.g. regulatory capture to provide profits when they may not actually be deserved-warranted - say by trying to get approval for a fraudulently approved product, e.g. "... the 26 pharmaceutical companies paid some $33 billion in fines during the 13-year period. The top 11 alone accounted for $28.8 billion" - https://www.pharmaceuticalprocessingworld.com/gsk-pfizer-and...
And arguably this is just the tip of the iceberg and the industry hasn't been held accountable for most of their fraud since the industrial complex formed.
This isn't just a problem with the pharmaceutical industry but with clearly corrupt-captured regulators like the FDA - who allowed this fraud to happen to begin with, missing or not checking into whatever lies were presented for the fraud to occur and the products to make it to market.
And that's why headlines like "Moderna's mRNA cancer vaccine works better than expected" should be taken with extreme skepticism.
Very little about medical development is free market.
But otherwise, I always agree with people taking a default being skeptical approach to any medical news.
The current status quo system, sure, but it's passion of scientists, researchers, biologists who inevitably make discoveries - it's the industrial complex and those wanting to control, mainly for profits sake, that has changed the way it worked and solutions were found early on.