ACTIVE IMMUNOTHERAPY TO HUMAN CARCINOMA ASSOCIATED ANTIGENS

针对人类癌相关抗原的主动免疫治疗

• 批准号: 3808563
• 负责人: J KANTOR
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3808563
• 关键词: active immunization; carcinoembryonal antigen; carcinoma; gastrointestinal neoplasms; genetic library; genetic manipulation; glycoproteins; human tissue; humoral immunity; laboratory mouse; molecular cloning; monoclonal antibody; neoplasm /cancer immunotherapy; nucleic acid hybridization; polymerase chain reaction; recombinant DNA; southern blotting; tissue /cell culture; tumor antigens; vaccinia virus

Carcinoembryonic antigen (CEA) is a 180,000-dalton glycoprotein expressed on most gastrointestinal carcinomas and many other human carcinoma types. A 2.4-kb cDNA clone, containing the complete coding sequence, was isolated from a human colon tumor cell library and inserted into a vaccinia virus genome. This newly developed construct was characterized by Southern blotting, DNA hybridization studies and polymerase chain reaction analysis. The CEA gene was stably integrated in the vaccinia virus thymidine kinase gene. The recombinant was efficiently replicated upon serial passages in cell cultures and in animals. The recombinant virus expresses, on the surface of infected cells, a protein product recognized by a monoclonal antibody (COL-1) directed against CEA. Immunization of mice with the vaccinia construct was found to elicit a humoral immune response against CEA. Pilot studies also demonstrated that the administration of the recombinant CEA vaccinia construct was able to greatly reduce the growth in mice of a syngenic murine colon adenocarcinoma which had been transduced with the human CEA gene. The use of this new recombinant CEA vaccinia construct may thus provide an approach in the specific active immunotherapy of human gastrointestinal cancer and other CEA expressing carcinoma types.

癌胚抗原（CEA）是一种分子量为18万道尔顿的糖蛋白 在大多数胃肠道癌和许多其他人类肿瘤中表达， 癌症类型。 一个2.4kb的cDNA克隆，含有完整的编码区， 序列，从人结肠肿瘤细胞文库中分离并插入 一个牛痘病毒基因组。 这个新开发的结构是 通过Southern印迹、DNA杂交研究和 聚合酶链反应分析 CEA基因稳定整合 在牛痘病毒胸苷激酶基因中。 重组子 在细胞培养物中连续传代后有效复制， 动物 重组病毒在感染的细胞表面表达 细胞，由单克隆抗体（COL-1）识别的蛋白质产物 针对CEA。 用牛痘构建体免疫小鼠 发现引发针对CEA的体液免疫应答。 试点研究 还证明了重组CEA牛痘的施用 构建体能够大大减少小鼠中同基因 用人CEA转导的鼠结肠腺癌 基因 因此，使用这种新的重组CEA牛痘构建体可以 为人类特异性主动免疫治疗提供了一种途径， 胃肠癌和其它表达CEA的癌类型。