Step forward for precision medicine - personalised anti-cancer vaccine tested in patients
Anti-tumour immunity is often weakened by the immune escape mechanisms, such as immunoediting, that cancer cells develop during their progression. Immunoediting refers to various changes, including genetic and epigenetic modifications, and the expression of immuno-inhibitory surface molecules, that enable tumour cells to escape detection and clearance by the immune system. Two of the most critical questions in tumour immunology are how this can be prevented and whether it would be possible to “train” immune cells detection and kill tumour cells?
Personalised anti-cancer vaccines aim to trigger an immune response to the patient's individual mutation spectrum. In two recent independent studies, performed by Otto and colleagues and Sahin and colleagues, such an approach has been for the first time tested in a limited number of melanoma patients. In both studies, promising clinical benefits have been observed. The US group, lead by Catherine Wu at the Dana-Farber Cancer Institute in Boston, Massachusetts, created a vaccine based on 20 patients-specific mutated protein fragments or neoantigens. Cancer neoantigens are displayed on the surface of cancer cells, but not the patients other cells. This means an immune response against these neoantigens should only affect the tumour cells. Six patients with melanoma were treated with the vaccine post surgery. Out of the six, four showed no relapse even after 25 months post-vaccination. Two patients relapsed, but after a subsequent treatment with the anti-PD-1 (anti-programmed cell death-1) antibody pembrolizumab have experienced complete tumour regression.
The experimental approach adopted by the German group, lead by Ugur Sahin at the University of Mainz in Germany, was slightly different. They developed an RNA-based vaccine, consisting of sequences encoding 10 patient-specific mutated proteins. Thirteen patients were treated in this study. Eight diud not have detectable tumours at the moment of vaccination and remained relapse-free during the entire follow-up period, 12 to 23 months. Out of five patients with tumours at the moment of vaccination, tumours shrank in two patients. One of these patients relapsed during the study, while a third patient entered remission following treatment with pembrolizumab.
Overall, the studies provide solid evidence regarding the safety and clinical benefit of anti-cancer vaccines alone, or in combination with other treatments, such as PD-1 blockade. This is a new step towards a more precise and personalised treatment strategy against cancer and other diseases.
Ugur Sahin is an invited speaker at the 25th ESGCT Annual Congress in Berlin.
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