肿瘤基因工程纳米乳剂疫苗的药效学研究
摘要
恶性肿瘤严重威胁人类生命和健康。恶性肿瘤的三大传统疗法-手术、放疗和化疗，治疗效果并不理想。随着免疫学、细胞生物学及分子生物学的飞速发展，肿瘤疫苗的研制与应用已成为治疗肿瘤复发、转移的有力手段。但由于存在缺乏特异性肿瘤抗原和有效的抗原提呈，以及MHC限制性、肿瘤异质性、疫苗生物利用度差等问题，使得现有疫苗的免疫效果不尽人意。黑色素瘤抗原(MelanomaAntigen，MAGE)是首先被发现的人类肿瘤特异性抗原，MAGE-1是MAGE家族的重要成员之一，广泛表达于多种组织的肿瘤，而在除睾丸和胎盘外的正常组织中均不表达，是肿瘤特异性免疫治疗理想的靶分子。目前，基于MAGE-1的肿瘤疫苗能诱导MAGE-1特异性CTL的产生，在肿瘤免疫治疗方面倍受重视。热休克蛋白(HeatShock Protein，HSP)具有分子伴侣作用，参与肿瘤抗原的加工递呈，在诱导肿瘤免疫反应中发挥重要作用；最近研究表明，制备结核杆菌HSP70与目的抗原融合蛋白是提高疫苗效能的有效方法。超抗原SEA可有效激活CD4~+T细胞，协同加强肿瘤抗原的免疫效果。纳米载药系统是近年来蓬勃发展起来的全新的药物载体，可有效提高所载药物，特别是蛋白质药物的生物利用度，与传统载药系统相比有很多优点。
Tumor is a big threat against people's health and life. The available protocols such as surgery, radiotherapy and chemotherapy are far from satisfaction. With the progress in immunology, cellular biology and molecular biology, tumor vaccines are regarded as the most attractive method and play an important role in prevention and therapy of tumor. However, the potency of tumor vaccines is not so forceful. The lack of tumor specific antigens, the short of effective antigen-present, the limitation of MHC, the polymorph of tumor cells and the low bioavailability are the major factors. The melanoma antigen (MAGE) was the first reported example of tumor specific antigens. MAGE-1 is one important number of MAGE. MAGE-1, expressing in most malignant tumors but not in normal tissue except for testis and placenta, has been used as the ideal target. The MAGE-1 vaccines can induce specific CTL and show potency in tumor immunotherapy. As molecular chaperone, heat shock protein (HSP) participates in processing and presentation of tumor antigen and plays an important role in eliciting antitumor immunity. Recent researches have demonstrated that linkage
Tumor is a big threat against people's health and life. The available protocols such as surgery, radiotherapy and chemotherapy are far from satisfaction. With the progress in immunology, cellular biology and molecular biology, tumor vaccines are regarded as the most attractive method and play an important role in prevention and therapy of tumor. However, the potency of tumor vaccines is not so forceful. The lack of tumor specific antigens, the short of effective antigen-present, the limitation of MHC, the polymorph of tumor cells and the low bioavailability are the major factors. The melanoma antigen (MAGE) was the first reported example of tumor specific antigens. MAGE-1 is one important number of MAGE. MAGE-1, expressing in most malignant tumors but not in normal tissue except for testis and placenta, has been used as the ideal target. The MAGE-1 vaccines can induce specific CTL and show potency in tumor immunotherapy. As molecular chaperone, heat shock protein (HSP) participates in processing and presentation of tumor antigen and plays an important role in eliciting antitumor immunity. Recent researches have demonstrated that linkage
引文
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