I never once thought about it before but how do they select a target antigen for what is effectively a human cell? Maybe they could take a similar approach to Rabies or Prion Disease.
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.
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.
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.
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.
What you proposed just doesn’t feel like the sort of thing we’ve come to expect from modern medical research, if it was outright targeting selective genetic information then it would be banned in many many countries, and maybe it should be just for it’s potential to become a weapon. No other commercially available mRNA Vaccines ever touched human DNA in that manner. It has always been some other protein structure to be identified by the immune system.
BioNTech is doing something similar. Their approach (and likely also Moderna’s approach) works by first identifying mutations in protein coding genes in the cancer cells. Then, they target the resulting mutated protein (that is distinct from the same protein in non-cancer calls) with their vaccines.
I never once thought about it before but how do they select a target antigen for what is effectively a human cell? Maybe they could take a similar approach to Rabies or Prion Disease.
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.
Holy shit, this is a type of down to earth, factual and enlightening comment that we used to get in reddit! Thanks for this!
Thank you for the kind reaction.
I recently moved from Reddit to Lemmy (same username) and I took my comments with me.
Obligatory: username checks out
Seriously though, thank you!
edit …also: fuck cancer
Agreed. And I was happy the comment didn’t end with, “in 1998, Hell in a Cell…”.
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.
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?
They have to manufacture it unique to the individual. Luckily, manufacturing custom mRNA is not very expensive.
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.
Especially compared to normal cancer treatment
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.
Yes.
What you proposed just doesn’t feel like the sort of thing we’ve come to expect from modern medical research, if it was outright targeting selective genetic information then it would be banned in many many countries, and maybe it should be just for it’s potential to become a weapon. No other commercially available mRNA Vaccines ever touched human DNA in that manner. It has always been some other protein structure to be identified by the immune system.
deleted by creator
BioNTech is doing something similar. Their approach (and likely also Moderna’s approach) works by first identifying mutations in protein coding genes in the cancer cells. Then, they target the resulting mutated protein (that is distinct from the same protein in non-cancer calls) with their vaccines.