How does a personalised melanoma vaccine work?
A personalised melanoma vaccine reads the DNA of your tumour, creates a tailor-made vaccine and trains your immune system to recognise cancer cells. Combined with existing immunotherapy, it reduced the risk of recurrence or death by 42% in a large study where participants were randomly assigned to treatments.
The DNA of the tumour is read to identify so-called neoantigens: proteins found only on the cancer cells of that specific patient. Computer programmes then help select which of those proteins are best suited to train the immune system. Based on this, a tailor-made vaccine is produced, which teaches the immune system to recognise and attack those cancer cells.
The most advanced type is an mRNA vaccine, in which the mRNA is packaged in tiny fat droplets (similar to the approach used in COVID-19 vaccines). These fat droplets protect the mRNA and deliver it to immune system cells. Once inside, the mRNA gives the instruction to temporarily produce the unique tumour protein, so that the immune system can recognise it. One advantage of this type of vaccine is that it activates two types of immune cells at the same time: helper cells that amplify the signal, and killer cells that directly destroy tumour cells.
Such a vaccine is almost always combined with a checkpoint blocker, an existing medicine that releases the 'brake' on the immune system. This appears to work: in a large international study (INTerpath-0001), the combination of the vaccine intismeran autogene and the checkpoint blocker pembrolizumab reduced the risk of melanoma returning or of death by 42%, compared with the checkpoint blocker alone. This is currently the strongest evidence available for this type of vaccine. Based on available data, the vaccine does not add extra body-wide side effects to the existing treatment.
Not every patient responds equally well. Tumours can actively evade the immune system, and sometimes the vaccine targets only a small subset of the tumour proteins present, leaving the rest of the tumour untouched. Added to this, producing such a vaccine is time-consuming and only works for patients with a specific inherited characteristic of the immune system. Research is also under way into combining personalised vaccines with precision radiotherapy, but it is too early to draw conclusions from that.
This answer draws on two extensive overview studies, a large study and a smaller earlier study in which participants were randomly assigned to treatments, plus two additional sources on mechanism and delivery. The 42% reduction in risk comes from a study where participants were randomly assigned, which is strong evidence for the effectiveness of the combination treatment. The mechanistic part (how the vaccine works) is well supported but partly based on overview studies; cause-and-effect relationships at that level have not yet been fully proven in people. Results in cancers other than melanoma remain uncertain.
Does a long life come at the cost of fertility?
Genetic research shows a small trade-off in men: higher testosterone is linked to slightly more children and a slightly shorter lifespan. In women this testosterone effect has not been found, although fertility does decline clearly with age.