A personalized mRNA vaccine reduced the risk of skin cancer returning or the recipient dying by 42% when used alongside an immunotherapy drug, according to long-awaited results for what could become the first approved mRNA vaccine for cancer. Oncologists regard a risk reduction of 10% as substantial, says Kristen Radford, an immunotherapist at Mater Research in Brisbane. A more than 40% risk reduction “would send many researchers over the Moon”, adds Seth Cheetham, a geneticist at the University of Queensland in Brisbane, Australia. The personalized vaccine, called intismeran, is not designed to prevent skin cancer, or melanoma, from developing in the first place, but to stop it returning in people who have already undergone surgery to remove tumours.
As shown in the graphic, this is one of the personalized approaches. Simply the approach is as follows:
1. Get a sample of the tumor from the patient.
2. Sequence the DNA and determine what unique cancer mutations may be there.
3. Generate a mRNA using these mutations.
4. Place the mRNA in a package, such as a liposome, and inject in patient.
5. mRNA will generate these related protein, many of which produce cello surface targets.
6. The patients immune system will see these as antigens and attack cells with these Ag surface targets
7. Add a PD-1 blocker which insures that the immune system remains on and not turned off
8. Pray the immune system works on the cells targeted and does not explode on everything else.
Now the key here is personalizing the surface proteins. In reality if we can do this for many patients then we can get a reference set, and the identity of the correct one may be more easily done by antibody tests. Say a patient comes in, we have this database of targets based upon many prior patients. We can then have Ab targeted for each one of the gene mutations and can then simple use Abs targeted for them. From this we get in no time the mRNA profile, generate it, put in liposome and voila! Kind of.
In reality we must always be concerned about immune system over response, such as cytokine storms. I fell the full story is yet to unfold. One must remember CAR-T cell promises.
I have noted a similar approach but using antibody drug conjugates, ADCs. It requires a database of surface targets on cancer cells, and then generates polyspecific Ab with a conjugated drug.
But, and this is important, many cancers are "protected" by a tumor micro environment, TME, and one must break through that as well.
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