與病原體的抗原不同的是，腫瘤抗原傾向于引起弱免疫反應(yīng),，與自體抗原相當,。因此，獲得有效癌癥疫苗的一個可能途徑是,，識別更強效的,、廣泛表達的腫瘤抗原。
Pastor等人提出另一種方式,，在其中,，新的、因而也是強效的抗原在腫瘤中原位表達,，從而使得擴散的腫瘤病灶（從免疫學(xué)上來講）更像病原體,。這一策略利用定向的siRNA來抑制“無義介導(dǎo)的mRNA衰變”，它刺激新抗原的產(chǎn)生及其隨后被免疫系統(tǒng)的排斥,。
以腫瘤為目標的定向輸送受與siRNA相聯(lián)系的寡核苷酸適配子調(diào)控,。這種方法的臨床可行性曾在小鼠模型中進行了演示，在該演示中它比常用免疫方法更為有效,。 （生物谷Bioon.com）
生物谷推薦原文出處：
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.
