靶向免疫治疗与靶向化疗新制剂的抗肿瘤协同作用

项目名称： 靶向免疫治疗与靶向化疗新制剂的抗肿瘤协同作用

项目编号： No.81473166

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨红

作者单位： 苏州大学

项目金额： 50万元

中文摘要： 为整合主动靶向化疗和靶向免疫治疗的优势，我们已将阿霉素引入叶酸-半抗原靶向免疫制剂，并证实：阿霉素-异体蛋白可刺激机体产生抗阿霉素抗体，在癌细胞表面可形成叶酸受体-叶酸-阿霉素-抗体复合物，对体内产生抗体的动物抑瘤试验疗效好，表明将抗癌药作半抗原的靶向免疫制剂是可行而有效的。因此，拟进一步构建叶酸修饰氟尿嘧啶泡囊、叶酸-阿霉素、阿霉素-异体蛋白新型制剂，并经体内外研究证实：在荷肺癌动物注射阿霉素-异体蛋白后等待抗体产生期间，以叶酸修饰氟尿嘧啶泡囊控制癌症恶化；抗体产生后注射叶酸-阿霉素可标记固定的和游离的癌细胞，促使机体启动自身免疫防御,直至完全康复，并可防止肺癌的转移和复发，发挥化疗及免疫治疗的最大优势，全面整合药物外力和机体免疫系统内力协同作用，对肺癌标本兼治。为治疗肺癌提供新的研究思路和实验基础，并可推广应用于其他癌症。本项目创新性强，适用性广，具有重要的科学意义和应用价值。

中文关键词： 抗癌药；叶酸受体介导的主动靶向制剂；叶酸-半抗原靶向免疫制剂；免疫识别；自身免疫防御

英文摘要： In order to integrate the advantages of targeting immunotherapy and actively targeting chemotherapy, we have introduced an anticancer drug (adriamycin, ADM) to the targeting immunotherpeutic preparation with folic acid (FA) heptan and have demonstrated that the ADM-foreign protein could stimulate the organism to produce antibody against ADM, and that folic acid receptor (FR)-FA-ADM-antibody conjugate was formed on the cancer cell surface, and that the in vivo study of inhibition of cancer in animal which had produced antibody gave satisfactory therapeutic results, indicating the targeting immuno preparation using the anticancer drug as heptan was feasible and efficient. Therefore, we intend to further fablicate a novel preparation of FR mediated fluorouracil (5-Fu)-loaded niosomes with FA-ADM and ADM-foreign protein, and to demonstrate based on in vitro tests and in vivo studies on lung cancer bearing animal that during the period of formation of the antibody via the injection of ADM-foreign protein, FA modified 5-Fu-loaded niosomes are utilized to control the deterioration of cancer. When the antibody has produced, injection of FA-ADM can mark the fixed and free cancer cells and stimulate the organism to activate autoimmno defense until the organism completely recover， and metastasis and recurrence of lung cancer can also be prevented. Thus the advantages of chemotherapy and immunotherapy can be most employed and a better integration of the synergistic function of the external force of drug and the internal force of autoimmuno function of the organism would be achieved so as to treat both principal and secondary aspect of lung cancer. This project provides a novel research design and will perform the experimental foundation for treatment of other types of cancer; thus it embodies significant innovation and broad applicability with important scientific significance and application prospects.

英文关键词： anticancer drugs;folate receptor-mediated active targeting preparation;folate-targeted hapten immuno-reagent;immune recognition;autoimmune defense