Melanoma: the personalised vaccine works – a potential breakthrough in treatment (costs permitting)
The personalised mRNA therapeutic vaccine has successfully completed a large Phase 3 trial. The results, presented at the EMO Congress in Madrid, open up a new frontier in the fight against cancer, with Italia playing a leading role.
Key points
A vaccine tailored to the individual patient, capable of teaching the immune system to recognise the tumour and fight it even after surgical removal, is finally a reality. This is demonstrated by the results of a large phase 3 clinical trial, INTerpath-001: in patients who had undergone surgery for melanoma but were at high risk of recurrence (stages II–IV). In particular, the risk of recurrence was reduced by 42 per cent and the risk of distant metastases by 38 per cent.
The study presented at the ESMO congress
The news comes from the European Society for Medical Oncology (ESMO) Congress in Madrid, where the results of INTerpath-001, an international randomised trial involving 1,137 patients, were presented. At two years, 82.2 per cent of patients treated with the autologous Intismeran vaccine, combined with pembrolizumab immunotherapy, were alive and recurrence-free, compared with 70 per cent of those treated with immunotherapy alone. The probability of being alive without distant metastases was also higher with the vaccine-immunotherapy combination: 88.5 per cent compared with 80.2 per cent.
This is a historic achievement because it is the first time that a phase 3 trial has demonstrated the efficacy of a therapeutic vaccine against this cancer. The study will be published shortly in the New England Journal of Medicine.
How does a vaccine work against a tumour that has already developed?
The principle is completely different from that of traditional vaccinations, which are used to prevent infections. “In this case,” explains Michele Del Vecchio, Head of Medical Oncology (Melanoma), IRCCS National Cancer Institute Foundation in Milan and lead recruiter for the study – “this is a ‘therapeutic’ vaccine, administered after surgery to help the immune system eliminate any residual tumour cells that could lead to future relapses”.
The technology is that of messenger RNA (the same as that used in Covid-19 vaccines), but it is used for a completely different purpose. The tumour tissue is sent to the USA, to Moderna’s laboratories, where the tumour’s DNA is analysed and the mutations capable of generating abnormal proteins (the ‘neoantigens’) are identified; this establishes a sort of molecular identity card for the cancer, unique to each patient. Based on this information, a personalised vaccine is produced, containing synthetic mRNA that encodes up to 34 neoantigens. This ‘tailor-made’ vaccine is then sent to the centre where the patient is being treated. The aim is to ‘train’ T-lymphocytes – the specialised soldiers of our immune system – to recognise and attack cells that display those targets. Each patient therefore receives a vaccine designed specifically for the characteristics of their own tumour, rather than a ‘one-size-fits-all’ product.
