L523S, an RNA-binding protein as a potential therapeutic target for lung cancer.
L523S, an RNA-binding protein as a potential therapeutic target for lung cancer.
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DOI：
10.1038/sj.bjc.6600806
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发表时间：
2003-03-24
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
基于疫苗的人类癌症免疫治疗方法可能最终需要肿瘤特异性和免疫原性的靶标。为了产生针对肺癌的特异性抗肿瘤免疫应答，我们已经寻找了可以作为辅助疫苗治疗靶向的肺癌特异性蛋白。通过使用cDNA消减和微阵列分析的组合，我们以前报道了KOC家族中的RNA结合蛋白L523S在肺鳞状细胞癌中过表达的鉴定。我们在这里展示了L523S在肺癌疫苗免疫治疗方面的巨大潜力。L523S作为一种癌胚蛋白，在早期胚胎组织中正常表达，但在非小细胞肺癌中有很高比例的重新表达。使用实时PCR、蛋白质印迹和免疫组织化学分析进行mRNA和蛋白质测量，证明了L523 S在肺癌中表达的特异性。此外，我们表明，L523S的免疫耐受性是自然打破肺癌患者，证明了可检测的抗体反应重组L523S蛋白在17个肺癌患者的肺胸腔积液中的8。总的来说，我们的研究表明，L523 S可能是人类肺癌恶性进展的重要标志物，并进一步表明，基于L523 S作为免疫原性靶点的治疗方法值得追求。
Approaches to vaccine-based immunotherapy of human cancer may ultimately require targets that are both tumour-specific and immunogenic. In order to generate specific antitumour immune responses to lung cancer, we have sought lung cancer-specific proteins that can be targeted for adjuvant vaccine therapy. By using a combination of cDNA subtraction and microarray analysis, we previously reported the identification of an RNA-binding protein within the KOC family, L523S, to be overexpressed in squamous cell cancers of the lung. We show here that L523S exhibits significant potential for vaccine immunotherapy of lung cancer. As an oncofetal protein, L523S is normally expressed in early embryonic tissues, yet it is re-expressed in a high percentage of nonsmall cell lung carcinoma. The specificity of L523S expression in lung cancer was demonstrated by both mRNA and protein measurements using real-time PCR, Western blot, and immunohistochemistry analyses. Furthermore, we show that immunological tolerance of L523S is naturally broken in lung cancer patients, as evidenced by detectable antibody responses to recombinant L523S protein in eight of 17 lung pleural effusions from lung cancer patients. Collectively, our studies suggest that L523S may be an important marker of malignant progression in human lung cancer, and further suggest that treatment approaches based on L523S as an immunogenic target are worthy of pursuit.
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影响因子：
4
作者：
Siomi, H;Dreyfuss, G
通讯作者：
Dreyfuss, G
DOI：
10.1084/jem.189.7.1101
发表时间：
1999-04-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Zhang JY;Chan EK;Peng XX;Tan EM
通讯作者：
Tan EM
影响因子：
30.8
作者：
REIJO, R;LEE, TY;PAGE, DC
通讯作者：
PAGE, DC
影响因子：
2.6
作者：
Mueller-Pillasch, F;Pohl, B;Gress, TM
通讯作者：
Gress, TM
影响因子：
8
作者：
MuellerPillasch, F;Lacher, U;Gress, TM
通讯作者：
Gress, TM