The main reason why tumours are not controlled by the immune system is that, 
unlike pathogens, they do not express potent tumour rejection antigens (TRAs). 
Tumour vaccination aims at stimulating a systemic immune response targeted to, 
mostly weak, antigens expressed in the disseminated tumour lesions. Main 
challenges in developing effective vaccination protocols are the identification 
of potent and broadly expressed TRAs and effective adjuvants to stimulate a 
robust and durable immune response. Here we describe an alternative approach in 
which the expression of new, and thereby potent, antigens are induced in tumour 
cells by inhibiting nonsense-mediated messenger RNA decay (NMD). Small 
interfering RNA (siRNA)-mediated inhibition of NMD in tumour cells led to the 
expression of new antigenic determinants and their immune-mediated rejection. In 
subcutaneous and metastatic tumour models, tumour-targeted delivery of NMD 
factor-specific siRNAs conjugated to oligonucleotide aptamer ligands led to 
significant inhibition of tumour growth that was superior to that of vaccination 
with granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing 
irradiated tumour cells, and could be further enhanced by co-stimulation. 
Tumour-targeted NMD inhibition forms the basis of a simple, broadly useful, and 
clinically feasible approach to enhance the antigenicity of disseminated tumours 
leading to their immune recognition and rejection. The cell-free chemically 
synthesized oligonucleotide backbone of aptamer-siRNAs reduces the risk of 
immunogenicity and enhances the feasibility of generating reagents suitable for 
clinical use.