Hacker News Reader

Comment by vibrio | Hacker News Reader

"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.

View on HN

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.

"proof of concept on the safe use of mRNA."

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.

Gonna need a citation on ADE taking time to discover. It’s typically caught in trials and we can run trials much faster during a pandemic.

Typically caught in animal trials even, and surely something that would've been caught already with the amount of people already vaccinated.

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.

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.

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.

It makes sense to me now why this team was so well-positioned to quickly respond to the novel coronavirus.

An individualized vaccine for cancer has to be created and administered fast, within the course of a specific patient’s cancer treatment.

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.

Oh I get it that is clever.

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.

> so received limited focus on that until SARS-COV-2

Or more accurately, until Bill Gates invested and retargeted them at vaccines. These investments predated Covid19 and were in 2015 and 2019.

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.

The Gates foundation granted money and invested, but not with that purpose.

Moderna:

https://www.gatesfoundation.org/about/committed-grants?q=mod...

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"

BioNTech:

https://www.gatesfoundation.org/about/committed-grants?q=bio...

2020: "To development of a COVID-19 therapeutic approach"

There was also a 2019 investment in BioNTech to develop an HIV vaccine.

Reply on news.ycombinator.com