一种高免疫原性抗胃泌素释放肽核酸疫苗的构建及其在体内对前列腺癌移植瘤的抑制作用  

A DNA Vaccine Targeting Gastrin-Releasing Peptide with High Immunogenicity and Its Inhibitory Action on the Growth of Prostate Carcinoma in vivo

作　　者：鲁勇[1] 王华倩[1] 欧阳可栋[1] 张会勇[1] 胡向兵[1] 李泰明[1] 曹荣月[1] 刘景晶[1] 

机构地区：[1]中国药科大学生命科学与技术学院,南京210009

出　　处：《药物生物技术》2009年第5期393-398,共6页Pharmaceutical Biotechnology

基　　金：国家自然科学基金资助项目(NO.30672464;30701023;30872393;30772570)

摘　　要：对多株肿瘤细胞的研究表明胃泌素释放肽（GRP）可作为生长因子刺激多种肿瘤的生长，并提示GRP可作为肿瘤免疫治疗的靶点。该研究构建了一系列抗GRP的核酸疫苗以激活针对GRP特异性的体液免疫应答，达到阻断GRP的目的。为打破机体已建立的GRP免疫耐受，将6个串联重复的B细胞表位GRP18～27作为抗原插入到真核表达质粒载体pCR3．1中，并辅之以多种免疫分子佐剂以达到增强核酸疫苗免疫原性的目的。构建的抗GRP核酸疫苗免疫小鼠后，pCR3．1-VS—HSP65-TP—GRP6-M2免疫组诱导出的特异性针对GRP的抗体滴度显著高于其它疫苗免疫组，并在随后的体内抗肿瘤实验中显著的抑制了GRP依赖性的RM-1移植瘤的生长。构建的这种高免疫源性和高效抑制肿瘤生长的抗GRP核酸疫苗为针对GRP依赖性的肿瘤及其并发症的免疫疗法提够了一种新的策略。Over the last two decades, several lines of experimental evidence have demonstrated that the gastrin-releasing peptide （GRP） may act as a growth factor in many types of cancer, suggesting that GRP might he a putative target for immunotherapy in neoplastic diseases. In this investigation, anti- GRP DNA vaccines have been designed to induce specific deprivation of GRP by strong humoral immune response. To break the already established tolerance of this self-peptide in vivo, 6 copies of the B cell epitope GRP18-27 in linear alignment （GRP6） have been inserted in a eukaryotical expression vector （pCR3.1） as immunogen. Furthermore, tandem repeated GRP18-27 was fused to different immunoadjuvants to optimize its immunogenicity. Immunization of mice with pCR3.1 - VS- HSP65 - TP- GRP6- M2 elicited much higher levels of specific anti-GRP antibodies and effectively inhibited the growth of a GRP-dependent tumor RM - 1 in vivo. The highly immunogenic and potent anti-tumorigenic activities of the anti-GRP DNA vaccine offered a novel immunotherapeutic approach in the treatment of the GRP-dependent tumor and its complications.

关 键 词：胃泌素释放肽 核酸疫苗 前列腺癌 

分 类 号：Q591.3[生物学—生物化学] R967[医药卫生—药理学]