A personalized, tailored cancer vaccination that induces complete rejection of established aggressively growing tumours in mice is demonstrated in this week's scientific journal Nature.
Identification of tumour-specific mutations that can be recognised by immune cells enables the development of vaccines that can encourage the immune system to target these mutations. This tailored immunotherapy approach could potentially be used as a blueprint for a broadly applicable strategy for personalized cancer treatment.
Tumour-specific mutations are ideal targets for cancer immunotherapy as they can potentially be recognized by the body’s immune system. However, every patient’s tumour possesses a unique set of mutations that must first be identified, which means that targeted vaccine approaches need to be individually tailored.
Researchers Ugur Sahin and colleagues of the Johannes Gutenberg University in Germany identify tumour-specific mutations capable of inducing immune responses in mouse models of lung, skin and colon cancer. They show that a large fraction of these mutations can be recognised by immune cells called CD4+ T cells.
They then generated vaccines to delivere customized synthetic mRNA sequences, which encourage CD4+ T cells to attack the target mutations, and showed improved survival in mice treated with the vaccines relative to untreated mice.
Finally, the researchers identify a similar abundance of mutations that can be recognised by CD4+ T cells in human cancers, which suggests that this approach may be applied widely.
Based on the findings of this study and their prior work, a first-in-concept trial in melanoma patients has been initiated and is recruiting for ongoing clinical trial.