Moderna's mRNA cancer vaccine works better than thought
freethink.com
freethink.com
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.
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.
Most recover nearly completely, but they all suffer some permanent effects, like sun sensitivity, hair loss, digestive problems, anemia, weakened immune system, etc.
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.
Long Island has historically had quite terrible air quality, as well, no?
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.
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...
It beats being dead, surely.
We didn’t start testing neoantigen mRNA cancer vaccines until 2017 [1].
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.
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.
Maybe the real surprise for some is that not everything was invented in the valley.
"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."
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.
The problem was that almost everyone who got the vaccine also caught the disease.
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.
> 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.)
The Wuhan strain wasn't that relevant even before the vaccines were widely available.
> Unfortunately, it turned out to mutate quite rapidly (like the flu) and soon the battles weren't always a rout.
Which was predicted and expected all along.
> It still reduces severity, though, and thus is still used.
Only if you take really awful studies seriously.
Nobody bothered to test this hypothesis in a proper trial.
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.
No purpose except for actually knowing whether it actually reduces severity.
> 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.
The sad reality is that you can't do matched population without a randomized controlled trial. You can't control for confounders you don't understand.
A recent hillarious example is the well-publicized paper that showed a drop of over 90% in Covid-related mortality after the first booster. Other researchers managed to obtain the data and it turned out there was also a similar drop in non Covid related morality. This resulted in the following correspondece, which is well worth reading:
https://www.nejm.org/doi/full/10.1056/NEJMc2306683
A choice quote from the authors of the original paper:
> During the B.1.617.2 (delta) wave in the United States, similar associations were observed between the use of mRNA vaccines and lower mortality not related to Covid-191 and mortality from any cause.
They mean that many of the studies showing a drop in Covid mortality after the mRNA vaccines, also showed a similar drops in non-Covid related mortality. In other words, the vaccinated population were healthier at the outset and the drop was bogus.
You need a proper clinical trial here to make this claim, as the observational data is ridiculously confounded.
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.
The vaccine works by instructing the body to make up to 34 “neoantigens.” These
are proteins found only on the cancer cells, and Moderna personalizes the
vaccine for each recipient so that it carries instructions for the neoantigens
on their cancer cells.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
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.
> immediately publish details and surrender any patent
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.
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.
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.
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.
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?
And if existing tech works well enough — great! Then use it, and don't use the more expensive mRNA ones.
Of course, there are benefits to mRNA vaccines, which is why they were deployed first — Moderna had a working vaccine barely over a month after starting work on it, with only the gene sequence of the virus from Chinese labs to work with. All the rest of the time was just testing. Effectively being able to print a vaccine given a gene sequence is extremely useful.
And again — the state (aka the United States) does not fully fund research. It provides less than half of funding in a non-banner year, and a fraction in boom years. Cutting funding not only would hurt deployment and development, it would also harm fundamental research.
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.
But otherwise, I always agree with people taking a default being skeptical approach to any medical news.
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.
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.
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.
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.
Don't get me wrong, it saved a lot of lives. Compared to every other vaccine we've all taken in our lives it's the absolute bottom of the barrel, and the fact that politically (and possibly for public health reasons) a good portion of politicians effectively lied about that made it so companies didn't feel like they should invest in making a better vaccine. I've had Covid twice and both times I was very sick - I'd love a better, more broad, vaccine.
I'd argue it's definitely not as effective as flu vaccines vs omicron. On a good year the flu vaccine can prevent 50% of flu cases in those that take it. Everyone I know has gotten Covid, vaccinated or not.
Omicron was considerably more virulent than flu - the risk of getting an infection is also a function of prevalence.
I'm not arguing that vaccines can't or shouldn't be much better. Just that they actually were considerably good if we take everything we should into account.
Sure, another example is the flu vaccine as you mention. The primary aim of the flu vaccine in the U.S. medical system is to protect high-risk people from life-threatening symptoms, even during infections from different strains.
Another example is the shingles vaccine. The primary aim is to prevent severe symptoms (such as neural damage and long term pain) during a reactivation of an existing chronic infection.
> It’s insane we’re changing the definition of words
The semantic meaning of the word vaccine hasn't changed. All that's changed is the U.S. CDC official definition text, to clarify that the primary aim of vaccines is to activate the body's immune system, rather than solely to prevent a new specific infection.
If you're curious about the language exactness, beyond the U.S. CDC, the U.S. FDA is also involved. For example, the U.S. FDA during COVID stated that a vaccine would need to be at least 50% effective for diminishing the severity of COVID-19 symptoms to obtain regulatory and marketing approval. In other words, the primary aim was to help people reduce damage; the primary aim was not to full-stop prevent infection.
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.
>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.
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...
I have no commercial interest in any of this, and my opinion is that any definition of "gene therapy" which includes mRNA vaccines is overly broad. "Change the host genome" is clearly what the average person things when they hear "gene therapy", and legal definitions should match that.
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.
If you think of the gene in RNA form (transcribed from DNA), it's a gene being translated to aminos. The gene is therapy.
I get gene therapy isn't used that way but I was trying to fairly interpret what people could mean.
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.