中文摘要：

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。

英文摘要：

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.