Moderna and Merck Announce an Investigational Personalized mRNA Cancer Vaccine

The mechanism is:

"mRNA-4157/V940 is a novel investigational messenger ribonucleic acid (mRNA)-based personalized cancer vaccine consisting of a single synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient's tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity."

Cancer cells typically have a lot of mutation at the DNA level, so the proteins they naturally emit or coat themselves with have mutant bits. If these mutant proteins can be used as targets for the immune system they are called neoantigens.

So I think the idea is to cause the manufacture of a lot of these neoantigen molecules to act as training targets for the patients immune system - like a regular vaccine. The immune system should get really good at attacking anything emitting the antigens, causing a powerful response against the cancer cells that naturally emit them.

The interesting thing about this vaccine is that it is a personalized medicine - each patient gets their own personal vaccine based on the random mutations found in their unique cancer DNA. Presumably this allows a wider set of targets than therapies targeting common 'shared' neoantigens.

There are probably some worries around personalized immunotherapies, because if every vaccine is unique to the patient, every new patient is kind of a first in man treatment. When the immune system goes wrong, it goes really wrong. With that said, existing treatments for very ill people can be quite dangerous so a new treatment only needs to be less dangerous for a given level of effectiveness.

Here is a nice summary that talks about the state of this kind of thing: https://www.frontiersin.org/articles/10.3389/fimmu.2021.6723...