与病原体的抗原不同的是，肿瘤抗原倾向于引起弱免疫反应，与自体抗原相当。因此，获得有效癌症疫苗的一个可能途径是，识别更强效的、广泛表达的肿瘤抗原。
Pastor等人提出另一种方式，在其中，新的、因而也是强效的抗原在肿瘤中原位表达，从而使得扩散的肿瘤病灶（从免疫学上来讲）更像病原体。这一策略利用定向的siRNA来抑制“无义介导的mRNA衰变”，它刺激新抗原的产生及其随后被免疫系统的排斥。
以肿瘤为目标的定向输送受与siRNA相联系的寡核苷酸适配子调控。这种方法的临床可行性曾在小鼠模型中进行了演示，在该演示中它比常用免疫方法更为有效。 （生物谷Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature08999
Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay
Fernando Pastor1, Despina Kolonias1, Paloma H. Giangrande2 & Eli Gilboa1
Department of Microbiology & Immunology, Dodson Interdisciplinary Immunotherapy Institute, University of Miami Miller School of Medicine Miami, Florida 33134, USA
Department of Internal Medicine and Department of Radiation Oncology, Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa 52242, USA
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 TRAs1, 2, 3 and effective adjuvants to stimulate a robust and durable immune response4, 5, 6. 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)7, 8, 9, 10. 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 cells11, 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.
