【作者】 段红；

【导师】 李少林；

【作者基本信息】 重庆医科大学 ， 药理学， 2006， 博士

【摘要】 食管癌(esophageal cancer)是人类常见的一种消化道肿瘤,分别占我国和世界恶性肿瘤发病的第四位和第七位。世界上70%的食管癌发生在我国,我国是世界上食管癌死亡率最高的国家之一。食管癌患者的五年生存率始终徘徊在10%左右,仍然严重威胁着人民的生命和健康。食管癌的治疗以外科根治性手术为主,但对于手术不能切除的晚期肿瘤和转移复发的肿瘤临床尚无有效的治疗手段,而肿瘤的导向治疗可以达到特异地杀伤癌细胞,并尽可能降低对正常细胞的毒副作用,提高抗肿瘤的疗效。近10余年来,肿瘤的生物治疗已作为一种重要的治疗模式被广泛研究和应用于临床。抗体介导的肿瘤免疫显像和免疫治疗是生物治疗的重要组成部分,对肿瘤及其转移的诊断、精确的分期和治疗方案的确定均有重要意义。自1975年Kohler和Milstein成功的制备第一株单克隆抗体以来,单抗的研究经历了鼠源性抗体人源化改造、小分子抗体和抗体展示文库三个研究阶段。其中抗体文库的出现将基因工程抗体的发展推向了高潮。针对鼠源性单克隆抗体在临床应用中经常发生的异源性问题和导向治疗中大分子抗体存在的穿透力较差的问题,我们尝试应用噬菌体抗体库技术构建食管癌相关的人源单链抗体文库,并用食管癌细胞对抗体文库进行了初步筛选。更多还原

【Abstract】 Esophageal cancer is one of the most common malignant tumors of digestive system in human. The incidence rate in malignant tumors is situated in fourth in our country and situated in seventh in the world. Our country is one of the countries with highest of esophageal cancer death rate, 70 percent of esophageal cancer were happened in our country in the world. The five year survival rate of esophageal cancer wandered 10 percent all the time, which threatened the people’s life and health. The curative surgical operation is the most important therapeutic approach for esophageal cancer. But there are still no effective measures for those advanced unresectable tumors and metastatic or recurrent ones. During the past ten years, cancer biotherapy has become an important therapeutic model used extensively in clinical and experimental fields. Antibody-mediated tumor immunoscintigraphy and immunotherapy are critical parts of biotherapy and have vital sense for diagnosis of cancer, metastasis, fine tumor staging and decision of therapeutic approaches. To overcome the problem of xenogenicity occurred in repeat clinical usage of murine antibodies and the low penetrance of intact antibody in targeted therapy, we constructed a human single-chain antibody library using phage display techniques from lymph nodes of esophageal cancer patients and screened this library with Eca109 cell line.更多还原