Hi,
How do cancer vaccines actually work? If I inject a peptide neoantigen into a mouse, what happens to it? Is it engulfed by the antigen presenting cells? if so, is it then presented on MHC class II? What if the neoantigen was initially presented on MHC class I and does not bind MHC class II? I know that alternatively I can deliver dendritic cells pulsed with peptides presented on MHC-I but I would be interested in tracing the steps of injected peptides. Also, some cancer vaccines are delivered as DNA/RNA - what happens in this case?
Any comments would be much appreciated.
Best,
Martyna
I was just reading some literature that suggests that peptides from vaccines bind directy to MHC molecules on the cell surface of APC and other cells. Here comes my question, though: empty MHCs are unstable and not transported to the cell surface. Hence, the peptide binding groove of the MHCs at the cell surface is already occupied by a peptide. Do the cancer vaccine peptides compete for binding with already-bound peptides? Do they displace them from the peptide-binding groove if they have high affinity for MHC? Or is my thinking about this whole process wrong?
As far as I know there is only one approved anti-tumor vaccine which is Sipuleucel-T. Here, DCs are isolated from a patient and then treated with the tumor antigen ex vivo and finally reinjected. This vaccine is rather inefficient and I think it is no longer available but several others that work this way are in late clinical trials.
One of the untargeted mRNA-based vaccines which just relied on injecting an encapsulated RNA failed in clinical phase IIb last year (developed by CureVac). I don't know whether there are more successful approaches in the pipeline.
As you already mentioned, targeted delivery to DCs is a way to go if you want to have a vaccine that is based on an injection to circumvent isolating DCs from the patient. Most prominently, anti-CLR antibody - tumor antigen fusion proteins are used, most often against DEC205 or CD206 (DEC205 is in phase II). Alternatively, there is one vaccine that uses a mannan-MUC1 conjugate to target CD206+ cells, which is in early phase III.
These are the approaches that I am aware of. I don't think that there are vaccines in the pipeline that inject just a peptide or protein as you suggested initially.
In short, if you are vaccinating against cancer the reactions would follow the same steps as vaccinating against any other disease. What happens to the antigen depends on the strategy and the type of antigen.
As for DNA/RNA based antigens, I expect that there viral vector or transformation is used to start antigen production in the desired cell population such as DC:s which will result in presentation.
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