this post was submitted on 02 Jan 2024
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[–] viralJ 187 points 11 months ago (6 children)

The target antigens are from human cells, but they are human cells that mutated and hence became cancerous. What Moderna does, is it takes DNA from these cells, sequences it and finds where exactly the mutations occurred. A mutation means that there is a different sequence of amino acids in a protein, which in effect makes it a new and distinct antigen. This way, they select antigens that are present in the melanoma cells, but not in normal cells of the body. Then they take these mutated sites and use them to generate mRNA that will encode them all, be used to synthesise these mutated antigens, and train the immune system to react to them as alien antigens. The treatment described in this article is a combination of the mRNA vaccine with Keytruda, which is a cancer therapy based on an antibody. The antibody targets a protein from the PD-1 / PD-L1 axis. This axis is used by normal cells to tell the immune system not to attack those cells, because they are body's own cells. Cancer cells often mutate like crazy, but then exploit this PD-1 / PD-L1 axis basically to say to the immune system "nothing to see here".

As for Rabies, I think we already have pretty well working vaccines, so we're not really in a dire need for new ones.

As for prions, it would be tricky. The reason prions do what they do is not that they are mutated proteins, but misfolded proteins. This is to say they assume the wrong shape, even though the sequence of amino acids in them is the same as in the healthy version of the protein. And this in turn means that they were synthesised based on a healthy, unmutated version of mRNA. And this in turn means that there is no mutation that the Moderna vaccine strategy could employ to train the immune system to recognise that prion protein.

[–] madcaesar 56 points 11 months ago (2 children)

Holy shit, this is a type of down to earth, factual and enlightening comment that we used to get in reddit! Thanks for this!

[–] viralJ 35 points 11 months ago (1 children)

Thank you for the kind reaction.

I recently moved from Reddit to Lemmy (same username) and I took my comments with me.

[–] randomuser38529 15 points 11 months ago* (last edited 11 months ago)

Obligatory: username checks out

Seriously though, thank you!

edit …also: fuck cancer

[–] [email protected] 6 points 11 months ago

Agreed. And I was happy the comment didn't end with, "in 1998, Hell in a Cell...".

[–] [email protected] 14 points 11 months ago

It's not necessarily impossible to target prions but it doesn't seem trivial. The reason they're dangerous is specifically the incorrect shape because that shape changes interaction behavior with other biological molecules, and immune cells could theoretically test for that change in interaction. But that's more complicated than regular molecule recognition which immune cells normally do. There's probably research in trying to make immune cells handle that too, but I haven't seen any articles about it.

[–] StorminNorman 10 points 11 months ago

Just on the rabies bit, there has been a couple of trials using mRNA vaccines on rabies. They've shown promise as they have been shown to be quite effective, and the current rabies vaccines we have are expensive and time consuming to make.

[–] [email protected] 10 points 11 months ago (2 children)

If it's based off mutated dna do they have to tailor a vaccine to each case? Or do cells mutate the same way every time?

[–] [email protected] 15 points 11 months ago (2 children)

They have to manufacture it unique to the individual. Luckily, manufacturing custom mRNA is not very expensive.

[–] [email protected] 3 points 11 months ago

That's really cool that they can do that. Kind of reminds me of something out of Star Trek when they have to "synthesize a cure" or whatever for some space disease.

[–] [email protected] 2 points 11 months ago

Especially compared to normal cancer treatment

[–] viralJ 1 points 11 months ago

In general, mutations can happen anywhere on any gene, so every patient's cancer will have its unique signature of mutations. However, like in the evolution of organisms by natural selection, most random mutations will have a detrimental effect and the cells carrying it will die. Some of the mutations will be neutral and despite the change in the amino acid, the cells harbouring it won't survive better or worse than cells that don't have it. But a few mutations will make the cancer cells proliferate faster or evade the immune system better, which will lead to these cells surviving and ultimately overtaking the population of the cancer cells. The latter mutations often happen in the same places on the same genes, and in melanoma for example, in as many as 41% of cases the 600th amino acid in a protein called BRAF mutates from valine to alanine (so the code for that mutation is "BRAF V600E"), and BRAF is only one example of such genes that commonly mutate in the same position.

So to answer your question - I don't know Moderna's exact protocol, but my guess is that the tailored vaccine will contain a mixture of these commonly occurring mutations and some mutations that are unique to the patient.

[–] Hardeehar 0 points 11 months ago