this post was submitted on 02 Jan 2024
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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.
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.