It was done before when they used a inactivated HIV virus to cure a child with leukemia by reprogramming her T cells.
She was in the terminal stage of disease so hence the approval of the experimental treatment , we don't know the long term effects or why it did not work consistently in other patients.
The NYT article I linked to actually has two pages. The second page goes into more details on cost. Here's a direct link to both pages of the article: https://archive.md/Fwyo0
Here's the relevant quote:
> The Pennsylvania researchers said they were surprised to find any big drug company interested in their work, because a new batch of T-cells must be created for each patient — a far cry from the familiar commercial strategy of developing products like Viagra or cholesterol medicines, in which millions of people take the same drug.
> But Mr. Hoppenot said Novartis was taking a different path with cancer drugs, looking for treatments that would have a big, unmistakable impact on a small number of patients. Such home-run drugs can be approved more quickly and efficiently, he said, with smaller studies than are needed for drugs with less obvious benefits.
> “The economic model is totally acceptable,” Mr. Hoppenot said.
> But such drugs tend to be extremely expensive. A prime example is the Novartis drug Gleevec, which won rapid approval in 2001 for use against certain types of leukemia and gastrointestinal tumors. It can cost more than $5,000 a month, depending on the dosage.
> Dr. June said that producing engineered T-cells costs about $20,000 per patient — far less than the cost of a bone-marrow transplant. Scaling up the procedure should make it even less expensive, he said, but he added, “Our costs do not include any profit margin, facility depreciation costs or other clinical care costs, and other research costs.”
Yeah $20,000 seems very cheap for such a treatment.
Also there are biohackers who synthesize their own insulin and even COVID-19 vaccines and test it on themselves. Their work may cause them more harm than good, but it's their bodies and they're free to experiment on it however they choose. When somebody has a terminal illness and is facing imminent death the risk calculus is very different where even taking the bargain basement biohacker version of a medication may make sense. (Though obviously this particular treatment is a bit different because it uses a modified HIV virus)
The mRNA cancer vaccine they're developing is for people who already have cancer. It's targeted based on the specific tumour the patient has, and basically primes the immune system to attack the cancer cells. They can't even develop the vaccine until the patient has the cancer it's fighting against.
How does this work?
In the case of Covid, I understand (for some value of "understand") how they can make the cells create virus proteins, which then train the immune system without an actual infection to be ready for when the real virus strikes.
But if someone already has cancer cells, wouldn't all the proteins to train against already be in the body in the first place?
A cancer vaccine would work by priming the immune system to target the proteins that is mutated in the tumor cells, and killing the cells producing them.
In fact, the body does this regularly. Cells frequently mutate to divide uncontrollably in the body, but are nearly always suppressed by the immune system. It is only when the tumor somehow manage to bypass the immune system or the immune system is sufficiently weakened that cancers can spread.
IDK they used measles virus in the movie, but in mRNA they don't use virus at all. They just use lipid nanoparticle with mRNA, it can't replicate. It just delivers mRNA to cells and the mRNA is used by the cells as a boilerplate to manufacture some proteins. In case of SARS-COV-2 vaccine it's spike (s-protein), not the virus itself, not lipid particle protein RNA, just RNA for the spike alone. RNA is not stable, for our human proteins we constantly manufacture new RNA from DNA. So basically we send command to manufacture some spike proteins so that our immune system can learn to recognize and neutralize the spikes. The movie parallel is just on the surface but in reality it works differently. I'm not saying that you shouldn't start packing your zombie-apocalypse backpack though.
From poking around on the BioNTech website and their associated press releases and papers from people who work there, it seemed that their founding goal was to develop personalized gene therapies for cancer. (Do a biopsy, send it in, cook some mRNA, send back a shot...)
My understanding is there was basically a "hey, we can repurpose our stuff for something really important" moment. Which they did, enabling them to produce a working shot with unbelievable speed. (I read somewhere that sequenced sars-cov2 genome to first vaccine shot was something like 48h for them)
This leaves out the part where they were already working mRNA vaccines for other diseases, like influenza. They repurposed that work, much the same as moderna did to make their vaccine.
"next target"? has been a target since inception.
At Moderna or BioNtech Cancer and Gene Therapy were priorities during the last decade or so, with limited evidence of success as far as I can tell. Infectious disease is scientific low hanging fruit for this approach, but has been less attractive commercial opportunities, so received limited focus on that until SARS-COV-2. The did a good job executing on the vaccines, but I'm not giving much for these vaccines as proof of concept for scientific success in cancer or orphan disease gene therapy.
It's a large proof of concept on the safe use of mRNA. Sure, any given implementation might be harmful, but this is (so far) showing that it is not in itself a harmful process.
And there'll be mountains of cash poured into mRNA research now, so if cancer treatment is a viable path, there's a reasonable chance of some success here. But it won't be a cure-all. We use "cancer" as if it were a single disease, but it's really a large group of different diseases with "unwanted cell replication" as the common factor.
Until about a year ago, potential treatments took 5-10 years of safety testing before general population use. This stuff takes time for things like antibody-dependent enhancement to be found.
What we do know is those who are obese have bad outcomes to C19. I am not obese, got it a couple months ago, and recovered with just home rest. Now I test positive for the antibodies.
Nope. It has been explained several times that 5-10 years wasn't needed because that's how long the actual testing took. It was partly due to funding issues, partly due to administrative issues, etc. E.g. the review process has been accelerated for COVID through two measures:
- phase 1 & 2 could be done at once. Which increased risks for only those who participated in phase 2, obviously
- phase 3 was evaluated with a rolling review. I.e. the manufacturers didn't wait until phase 3 was over and submit their data then, but did it so continuously. And also FDA & EMA started to process those right away.
Then there is also the fact that when you don't have a pandemic (or even an epidemic) then it's hard to do a phase 3, because it will take a lot of time for enough people to get infected. Part of the reason the SARS1 vaccine was never finished (have never earned an authorization) is that it was over by the time the phase 3 would (or did) start. The same thing slowed down the ebola vaccine. The candidate was ready but then the outbreak vanished, so there was nowhere to do a phase 3.
What we do know is those who are obese have bad outcomes
That is such a blatant over simplification that it comes right up to the border of trolling, perhaps a bit over that border. It is incorrect on a level that practically defies any potential for a response due both to the impracticality of detailing here just how wrong it is, and the fact that a person who makes that sort of comment is unlikely to respond to anything argument that contradicts such a simplistic view of things.
I'll at least address your reference to ADE by pointing out there might be a theoretical possibility there, things have worked out just fine in other illnesses even when know it can be an issue in-- for example-- measles, and yet a vaccine still knocked that out of general circulation a while ago until falsified research helped spark the anti-vaxxer movement and it gradually crept back in to un-vaccinated pockets of the population. Further, ERD simply does not take 5-10 years to detect.
Congratulations on not being obese, and surviving Covid, but no one is debating the fact that most people don't die from it, so you've missed the mark significantly by using your own experience to justify your simplified view of the situation.
Now that it's been proven and the manufacturing scaled, there may be a fair bit of profit in it. If tuberculosis, MRSA, and even malaria can be targets, that would be world-changing.
I'm not even sure how "cancer" is really a target -- are they talking about individualized treatments for your specific cancer cells?
The process generally relies on discovery of potent neoantigens within the somatic mutations and then building mRNA to express it. So, yes, the idea is individualized treatment for cancer. I’m not sure there is any relevance for organism-scale immunity like TB/MRSA/malaria.
I imagine that the tumour would quickly evolve to repress expression, mutate, or completely delete the targetted neoantigen as the neoantigen is probably not required for viability.
This is absolutely true, and actually the mutations are usually quite diverse already, so it's thought that multiple neoantigens should be targeted simultaneously. However, no matter how much you target, the diversity and evolution of cancer always wins. Therefore, the goal is not to target every last cancer cell, but to trigger enough of an immune response across a wide enough variety of mutations for the B cells to adapt to whatever else they find. This is also the theory of checkpoint blockades, and they will probably be used together.
That's what it sounds like. Possibly safer and simpler than viral immunoconological vectors. I guess the issue is identifying the very specific histological anomalies in cancer cells to target SARS-CoV-2-spikes style. Perhaps this can be done by flow cytometry and sequencing of healthy cells vs. cancer cells. The big challenge is making certain no other cells share the targeted structures.
The time that mRNA vaccines will save compared to the effort people had to do to optimize data to fit in an adenovirus vaccine in itself can speed up science significantly.
About 50-100 different sicknesses are being targeted right now (a lot of them in secret), so we can't know the biggest winners yet.
This will be another tool next to radiation and chemotherapy to fight cancer; it won't be a cancer cure.
The problem is that every tumor is different. If the idea is to create a vaccine that attacks the tumor, it can be faster and easier with mRNA to develop an individualized vaccine.
I’m pretty sure the SARS-CoV-2 mRNA vaccines are based on mRNA vaccine research for the original SARS virus. The only reason that one wasn’t finalised is that the epidemic sort of died out on its own.
Which is why Bill Gates gave them money to continue that work.
IIRC it only took them about 3 weeks to create the vaccine. To work that fast they had to have had a good base to work from, the infrastructure to do so, knowledge and experience.
2016: "To develop a novel platform technologies for antibodies or vaccines to reduce HIV acquisition in developing countries"
2019: "To assess the feasibility of mRNA technology to deliver antibody combinations in selected neonates in low resource settings in order to reduce the impact of neonatal sepsis in this vulnerable population"
I know that they've made HIV a chronic condition rather than a deadly disease, but I'd still like to see it eradicated with a vaccine. Same for herpes and viral hepatitis. I hope they tackle all those in due time.
Yes there are, but it's only for the high risk sexually transmitted ones. There are some 100 strains of HPV, and there's no vaccine for the "common warts" you can get on hands, feet, knees. Although what's interesting is the getting a shot of a vaccine for STD HPV types can in some cases help body clear existing infection of common warts. https://pubmed.ncbi.nlm.nih.gov/31369771/
We need to stop tolerating these kind of tinfoil conspiration theories. It does not even make economical sense.
If you are the first to come up with a cure for that disease you will make huge profit compare to the rest of the industry. Especially if the cure involves coming up with a vaccine or a personalized treatment. Thats like the sustainable subscription wet dream of software companies.
Yeah, let's ignore facts. Let's ignore bankruptcies due to medical bills. Let's ignore $600 EpiPen -- never happened. Let's ignore that it may be cheaper to fly to another country for medical treatment, etc. It is all tinfoil conspiracy theories.
Here's a reminder: I was answering this:
"they've made HIV a chronic condition rather than a deadly disease, but I'd still like to see it eradicated with a vaccine."
note: HIV, no cancer.
There is an incentive to sell drugs for chronic conditions. Curing these conditions would cut into the profits for selling drugs for chronic conditions -- I hope it should be hard to misunderstood -- it is just a simple math (lifetime customer for chronic condition vs. a single purchase for the cure).
That's like monopolies, right? The ultra right argument is that they are harmless, because it's easy to disrupt them.
In practice that hardly works, due to nasty business practices and lobbying.
On the other hand this argument works better for scientific progress. Yes, company selling like insulin shots might not invest into curing diabetes. That does not mean that there is not plenty of researchers looking into that issue, potentially disrupting the market.
I just hate that this gets framed in a way that is just a step from conspiracy theories.
Cancer vaccines aren't unheard of or completely crazy - there's a Glioblastoma (GBM) cancer vaccine that's pretty far in development by Canadian bio VBI Vaccines that may see approval soon, upon completion of their phase 3.
https://en.wikipedia.org/wiki/HPV_vaccine
"It is estimated that HPV vaccines may prevent 70% of cervical cancer, 80% of anal cancer, 60% of vaginal cancer, 40% of vulvar cancer, and show more than 90% efficacy in preventing HPV-positive oropharyngeal cancers."
> The vaccine (...) uses messenger RNA, or mRNA, to carry instructions into the human body for making proteins that prime it to attack a specific virus.
I love how this technology turns a medical challenges into a software problem. Being able to code medicine will open up an affordable way to personalized drugs, instead of the current day "one size fits all" solutions. What a time to be alive!
But in practice: personalized medicine is impossible to tests. We rely upon giving tens of thousands of volunteers medicine ahead-of-time to prove if medicine is safe.
While the technology theoretically exists to make and distribute personalized medicine, the ethics and safety questions of doing so remain unanswered.
Personalized medicine has been tested for years in clinical trials. Trials require tens -- not tens-of-thousands -- of volunteers.
Personalized therapies are being used to treat cancer patients right now, and using machine learning to find the right binding site for a particular patient's tumor should present no more ethical questions than giving them NSAIDs.
That's really not how mRNA works. If DNA is the source code of our body, then mRNA is the machine code that exists in L1-instruction cache. (There's another process out there that copies DNA into more readily processable RNA)
The way any of this mRNA stuff works is by throwing instructions into our body to create certain proteins in certain configurations. For COVID19, the vaccine is... as XKCD-put it... a set of blueprints to build a "fake death star" without any weapons activated.
mRNA further has a "innate safety" mechanism, in that it degenerates. That's why our body uses DNA after all: because DNA does not degenerate, even though RNA is what's actually executing so to speak.
So any mRNA medicine will have to be strictly temporary, and get its job done in a limited timeframe. The COVID19 virus gets around this fact by self-replicating. The instructions that our cells execute are to create a new COVID19 virus. The original "quine", COVID19 (and all viruses) "print themselves" as part of their execution.
-------------
The "vaccine" is a set of blueprints for the COVID19 "spike protein" (and ONLY the spike-protein). Since it is missing all the other parts of COVID19, it cannot self-replicate. Our body then gets trained on recognizing the COVID19 spike protein, and is ready when the real thing attacks our body.
I believe there are also viruses who can insert themselves into the cells DNA, and there are some articles on how some parts of human DNA is already old virus genome. Viruses are far more dangerous in that regard.
There's both DNA viruses and RNA viruses. RNA viruses are way more common though.
> [DNA] Viruses are far more dangerous in that regard.
Not necessarily. "Corrupt DNA" can be somewhat detected the body as a cancer cell. Our "Natural Killer" cells then kill those cells.
Cancer / corrupted DNA happens all the time in our bodies. Even healthy bodies (!!). The difference between a cancer-patient and us however, is that a cancer-patient is overrun with cancer-cells.
Our bodies naturally kill off cancer under normal circumstances. Figuring out why cancer / corrupted DNA completely takes over the body is a big mystery, especially because our body is so good at fighting off cancer under normal conditions.
I mean, my point is that "if (race == whatever)" is completely nonsensical from an mRNA perspective.
There's no way for mRNA to scan the rest of your DNA sequence to make an if/else determination. mRNA is just gonna execute once its in the body.
> Or how about some biological ransomware?
Yeah, that's called a poison and antidote / antitoxin. You don't need mRNA for that. Poison someone's food, and as they lie dying, you can offer them the antidote in exchange for something.
When we say mRNA "executes", that's a cell injesting mRNA, and assembling a protein (polypeptide). For example, the mRNA sequence 'ACU', when 'executed' by a cell, will turn into a Threonine: https://en.wikipedia.org/wiki/Threonine
> There's no way for mRNA to scan the rest of your DNA sequence to make an if/else determination. mRNA is just gonna execute once its in the body.
Of course there is, genes can be turned on/off using transcription factors. Still, the sequence of vaccines are published and easy enough to sequence and analyze, so I don't think something like this could be mass produced.
A better analogy would be anonymous functions thrown into the global namespace that get called with whatever arguments that may happen to be on the stack at that moment.
I would first want it to work without side effects and give it time to study. The vaccine is less effective than sputnik vaccine. Given a choice, I would take sputnik 100 times over.
I don't quite follow. The whole shtick with problem cancers is that your immune system is ignoring them for whatever reason. mRNA vaccines work by priming the immune system for something it would attack anyway, but under safer circumstances since there's no real virus in the vaccine. What can the mRNA create that the immune system will train on given that the immune system isn't attacking the real thing to begin with?
(And to be clear, this obviously is a piece I'm missing rather than a hole I'm trying to punch in their work. They're way smarter than me and wouldn't be working on this unless they had a clear idea)
It sounds like you are conflating the antiviral implementation with what the mRNA technology itself is doing. mRNA acts as a blueprint for proteins. Your body has tRNA translation complexes that "read" the mRNA and appropriate the correct amino acid to add to the protein chain. Here is a more detailed description - translation begins about halfway down with the UGCAs: https://www.nature.com/scitable/topicpage/translation-dna-to...
So basically the mRNA tech is a means of delivering protein blueprints for in vivo production using your bodies natural machinery. In the case of COVID-19, this was used to manufacture spike protein, which attracts the body's immune response.
I'm not an expert on the best way to use the tech with cancer, but I could imagine a number of different approaches - targeted inducing of cell death, "painting the target" for chemo drugs, making things like monoclonal (designer) antibodies in-vivo, etc. The silver bullet is that it eliminates all of the complexity of creating and storing advanced biologics outside the body. Now you just deliver a bit of code and your body does it's thing.
> I could imagine a number of different approaches - targeted inducing of cell death, "painting the target" for chemo drugs, making things like monoclonal (designer) antibodies in-vivo, etc.
The article does explicitly call it a "cancer vaccine" (direct quote from the researcher) and says "the same principle [as the COVID-19 vaccine] can be applied to get the immune system to take on tumours".
That's more specific than sneaking in with mRNA to get the body to produce something. It definitely sounds like whatever it is, it gets the immune system involved. It seems fair to ask exactly how it does this.
The promise of mRNA is the potential to prompt the body to produce the therapeutic antibodies itself, rather than produce them externally and injecting regularly.
> That's more specific than sneaking in with mRNA to get the body to produce something.
No, it really isn't more than that. You could send mRNA code into the body that produces a designer antibody that is specific to the cancer a patient has (similar to CAR-T, Keytruda, etc.), or you could design mRNA that specifically causes cancer cells to express antigens that attract the immune system. I'm obviously oversimplifying a pinnacle of human achievement, but on paper it should work that way.
For certain definitions of distinct, yes. Not as distinct as a bacteria cell vs. a human cell, so you have to be more careful selecting a target. For example, antibiotics and chemotherapy both affect cell reproduction, but antibiotics have fewer major side-effects than chemotherapy - the targets on bacteria aren't present on human cells (though they are sometimes present in the good bacteria in your gut). Chemo targets cells that use the same mechanisms as health cells, thus the side effects. Since cancers are driven by mutations at the genetic level, the goal would be to find a specific mutated site (or a combination of sites) to target that would allow specific delivery of drugs or markers or whatever.
If you can find specific sites, you can design a complimentary piece of RNA code to bind it and allow the drug delivery mechanism to do it's thing. Way fewer side effects versus systemic delivery.
To a certain extent because they need to consume vast amounts of resources. It's not perfect though so it's generally assumed that every type of chemotherapy has collateral damage of some sort as regular cells also get accidentally killed.
cancer cells have distinctive traits that can be exploited for targeting [1]. A fairly elegant approach is to use a vesicle studded with antibodies to the tumor antigen to get the payload to the bad cells, the mRNA is then endocytosed into the tumor cell, expressed and the protien product adorns the tumor cell. when this is an antigen such one sees with measles there would be a long lasting immune response that would look for any cells with this antigen [i.e. target tumor cells]
I don’t know the biology, but mRNA vaccines has been used for cancer for some years now. I wish this message was louder and clearer because people seem to think covid is the first use of the technology.
My very basic understanding is you customise the mRNA payload towards the immune system targetting the mutating cells that have caused cancer in a patient (after the cancer material has been surgically removed). This prevents the cancer from re-occuring.
Use of mRNA is a much more generalized technique than just producing an immune response. In fact part of the problem in making them an effective delivery system for other therapeutics is trying to avoid triggering an immune response.
I believe the advantage of the mRNA method is that it’s somewhat generic: you can stick any (protein-coding) RNA fragment into it, and it will be expressed in the body and picked up as a target by the immune system if it has any potential for the latter (I. e. isn’t something that’s ubiquitous in the body already)
As such, it is faster to get from idea to vaccine. Recent history is an example already, but the cycle will be improved dramatically considering the technology is very much still in infancy. It’s also cheaper, to the point that producing ten doses of ten different vaccines may not be more expensive than producing a hundred doses of a single vaccine. This will be helpful against “cancer” which is closer to an unlimited number of different diseases than a single target.
I was wondering the same thing. Vaccination means exercising against a mockup foe before meeting the real enemy. But the cancer patient is already deep into the battle, how could adding mockup enemies help winning?
Perhaps the molecules they want the immune system to attack aren't sufficiently mobile, sticking to the tumor instead of diffusing into the entire body?
From what I've picked up in the pandemic the immune system has a dedicated proving ground spots where experimentation is happening, and relies on special cells to transport foe candidates into those proving grounds (just like a programmer would gather problematic input samples in their unit tests). Maybe the tumor bits they want attacked cannot be transported to "lab organ", but fragments created separately, from mRNA injections, could, and once the immune system is producing antibodies against those fragments they will also react with the immobile real tumor bits.
Purely speculative on my part, but maybe it really is something along those lines?
The core issue with cancer is that the immune system does not combat the tumor. Cancer patients suffer from damage caused by the tumor and by aggressive therapies.
Cancerous mutations happen all the time. Usually, the affected cells either
* repair the damage,
* get wrecked by the damage's side effects,
* suicide or
* get blasted by the immune system because the mutation alters their surface proteins in weird ways.
Tumors form because the cancerous mutations succeed to fly under the radar of the immune system. mRNA therapy can be used to make the immune system target specific surface features of cancer cells, or to do something else in connection with the cancer cells that attracts the immune system's attention.
Just a newbie question: Would it be beneficial that body itself generates transcriptional repressor proteins (via mRNA vaccine) that bind to specific cancerous mutation genes instead of giving some medicine that has similar inhibitory goals?
(Sorry, I'm just trying to learn cell biology on my own.)
it is difficult enough to target a cell and deliver to the cytoplasm, when you attempt to move further and deliver to the nucleus this is further difficulty.
if you are certain you have a specificly targeted delivery that stays away from non cancerous cells you can use mRNA to create labels [antigens] on the cell surface that the immune system interprets as pathogenic, thus immuno targeting oncocytes for destruction.
> The scientist who won the race to deliver the first widely used coronavirus vaccine says people can rest assured the shots are safe,
Ok. But did anyone expect her to say anything else?
This is obviously a (slightly?) veiled pitch for backers, more funding, and perhaps some regulatory freedom.
It's unfortunate that the media can't resist the temptation to pitch this as news. It's not. It's interesting. There's certainly intrigue at 50k ft. But you don't ask the cow, "What do you think of milk?"
Promise and hope should be tempered with context. We've been to this rodeo before.
Anyone more knowledgeable than myself following any of the research saying that the mRNA vaccines can be dangerous due to over/mis-expression, such as:
I'm not certain that anyone should be taking a "scientific paper" seriously that concludes with:
> Many have raised the warning that the current epidemic of
COVID-19 is actually the result of an bioweapons attack released
in part by individuals in the United States government
It concludes (regarding the claim) that "mRNA-based COVID-19 vaccines can cause prion disease leading to neurodegenerative diseases like Alzheimer’s dementia. What are prions, and can these vaccines cause prion disease? (Spoiler alert: The answer to the second question is almost certainly no. It’s speculation based on highly implausible biology.)"
Classen is correct in one respect at least: "the current RNA based SARS Cov-2 vaccine has been approved in the US on emergency order without long term safety testing." But I think we all know that and understand why.
Yeah. I couldn't find the other articles I was looking for.
His US bioweapon theory is pretty silly.
As for "anti-vaxers", though I don't count myself as one or probably agree politically with most of them, I'm going withhold complete judgment there - vaccines are obviously effective, but until there are actually epidemiologically valid multi-generational meta-studies with as many confounding factors as as possible removed (probably requiring placebos be given to a percentage of people) I'm not sure we can separate vaccines from other relatively novel environmental or behavioral factors that may lead to certain diseases, esp. developmental/neurological conditions.
I now have a bit less knee-jerk anti-anti-vax attitude after sitting at a table with several doctors who admitted they didn't/wouldn't follow all vaccine protocols with their own children - but I know this is certainly not scientific evidence.
But I'll certainly be getting the COVID vaccine when I'm eligible...
That's about the barest bit of research with a complete lack of details or stats on their methodology & results. I don't even see details on the specific sequences they claimed to identify. And for what it's worth, I also wasn't able to find the journal itself in any major index either.
Not plausible. Paper has no citations and is by an author who is anti-vaccine in general. Absolutely no other discussion of such a possibility in the field.
She was in the terminal stage of disease so hence the approval of the experimental treatment , we don't know the long term effects or why it did not work consistently in other patients.