Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay

Tumour antigens — unlike those of pathogens — tend to illicit weak immune responses, on a par with 'self' antigens. One possible route to effective cancer vaccines, therefore, is via the identification of more potent and broadly expressed tumour antigens. Pastor et al. present an alternative approach, in which new and hence potent antigens are expressed in tumour cells in situ, making disseminated tumour lesions — in immunological terms — more like pathogens. The strategy uses targeted small interfering RNA (siRNA) to suppress nonsense-mediated mRNA decay, which stimulates the production of new antigens and their subsequent rejection by the immune system. Tumour-targeted delivery is mediated by oligonucleotide aptamers linked to the siRNA. Clinical feasibility of the technique was demonstrated in a mouse model, where it was more effective than a commonly used vaccination protocol.