BioNTech presents positive phase 1/2 data for CAR-T cell therapy candidate

https://www.science.org/content/blog-post/mrna-vaccines-what...

Quoting from it: “ And that's what you see with the intramuscular dose as well: a good part of the dose goes to the liver, but in that case there's a substantial effect in the muscle tissue itself, and it's longer-lasting (out to about a week of protein expression)”

So, yes, an mRNA vaccine (the current ones, anyway) likely causes a fair amount of Spike protein to be expressed in your muscle tissue, but no one has noticed it causing the death of large amount of muscle tissue [0], and despite some searching, I haven’t found any evidence that anyone really understands what’s going on.

[0] People produce cytotoxic lymphocytes that detect bits of spike protein displayed by MHC1, much like CAR-T cells detect whatever they’ve been engineered to target on the surface of cells. Yet CAR-T (sometimes) kills massive numbers of tumor cells, and mRNA COVID vaccines apparently don’t cause the death of massive numbers of harmless cells that took up some of the vaccine. I’m curious why.

But sure, the study design and primary/secondary endpoints are always levers to increase likelihood of admission. There are often long discussions with the FDA and other regulators on how the endpoints and study population should look like.

Of course where we have other cancer treatments that works well those should be a first line (at least for now - who knows how this will advance), but all too often we don't have good options.

As a kidney transplant patient, I'm particularly interested in the latent virus vaccines like CMV, and EBV vaccines. Those who have an organ transplant have to deal recurrence of CMV, EBV and BK virus because they are quite common and latent in the body from past occurrences. I don't know if these vaccine will work on me anymore since I'm already immunosuppressed but there is hope. I'm dealing with both BKV and CMV right now. Treatment is mostly to cut back on immunosuppressants to let your immune systems fight back but that has its own risks. And I never had CMV before while so I'm dealing with those from my donor organ. There are some companies doing trials on antibody treatments right now.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530862/

Personally most people I know who don't want the covid vax reached that conclusion after weighing the risk/benefit.

I'm also from an area where "Pray" would be a significant part of their life, but has nothing to do with their decision.

Stop scaring people off with your othering, jerkface attitude.

History will be the judge as to whether you are right about a particular vaccine. They're not all the same in terms of efficacy nor safety, OBVIOUSLY.

However, it's impossible to prove that Covid is more harmful than the vaccine in every particular cohort of a population.

Anti vaxxers perceive themselves to belong to a cohort that are less likely to be harmed by the illness, because of youth, behaviour, or physical fitness or luck or religion or whatever.

On the other hand, they have plenty of evidence that people belonging to the same cohort have been adversely affected by the vaccine, therefore it's entirely logical from their point of view to not get vaccinated.

The current wave of anti SARS-CoV-2 vaccines skepticism has multiple facets and is also country dependent.

First, the risk profile of the disease meant that the best solution would be vaccinating those at risk immediately and leave the rest for judgement of the individual. However, people took the infamous Israeli study about 94% reduction of risk of asymptomatic infection (hence transmission affecting) at face value (the 5MM people from that study weren't swabbed regularly; it was an extrapolation), which meant that some tried to follow the dream of impossible elimination (impossible since March 2020) so they thought everyone needed to be vaccinated. Previous evidence on other CoVs was largely ignored.

Second, many vaccinated to go back to a normal life. Imagine the reaction when those people were faced with more lockdowns, masks, restrictions... Some thought they were made fun of.

Third, the government officials absolutely hated good news as they thought fear was good to achieve compliance, at least in UK and Italy. In Italy, not the nutjobs, but respected members of medical society unwillingly questioned the efficacy of vaccines ("half-work", someone said). This confused the general public even more

Fourth, adverse reactions are to be expected and with loads of inoculations, some are bound to appear even if very rare. Even more with these vaccines which are highly reactogenic. The confused reactions on the AZ vaccines when there were cases of thrombosis were eloquent. Also, risk vs benefit ratio was not considered. Children have very low risks but have a higher incidence of (rare) adverse events. Given this, the ratio isn't favorable, but it was pushed anyway without solid data (the confidence intervals on FDA documents for pediatric versions of these vaccines are horrid).

Fifth, some countries went out of their way to make the lives of those not vaccinating very miserable. In Italy you could not even work without three doses. Children without three doses > 12yo could not take the bus legally. And the whole Canadian truckers matter.

While antivaxxers are a very loud but small minority with no real power (they're extremists) the whole matter was a massive failure at scientific communication. Also because governments wanted to treat citizens like stupid peasants that needed guidance by the enlightened. Well, not all of them, but in Europe there were many.

It's possible Trump influenced what happened here, but I suspect this is at least a bit of Americo-centrism on your part...

If people die due to your inaction, you are not liable.

If people die due to your actions, you very much are.

Even a minor issue can end up being harmful. If you have a cancer treatment that's safe and effective, but you haven't fully vetted it and it turns out to be less effective than another available option, then your drug would cause harm.

It's safer to test these things, otherwise you get sued, go to jail, your company folds, and nobody gets cancer treatments anymore.

We need some process to distinguish between what works and what doesn't work.

The question isn't merely "how quickly can we get this one thing to market" it's "how can we prove that it works as quickly and cheaply as possible, without biasing us to treatments that don't actually work, and with giving all options their proper due."

For a while in machine learning there was a field called "active learning" (might still be ongoing?) that was all about how to choose the most informative questions to ask to learn as quickly as possible.

We face that same question with cancer therapies. Every patien that is on one trial can not be on a trial for a different therapy, so that's one limited resource for how quickly we can learn. But the other limited resource is of course how much we want to spend on validating therapies versus deploying existing, working therapies to a broader group of humans.