人造靶点免疫导向阿霉素对荷肉瘤小鼠瘤质量及生存期的影响

目的 制备小鼠抗人IgG-葡聚糖-阿霉素免疫靶向偶联物,在肿瘤组织中接种人IgG非特异性靶点,探讨人造靶点免疫导向治疗肿瘤的可行性.方法 制备小鼠抗人IgG-葡聚糖-阿霉素(阿霉素)偶联物,建立荷瘤小鼠模型.采用ELISA法测定小鼠抗人IgG-葡聚糖-阿霉素偶联物抗体活性;体外细胞毒性实验比较分析小鼠抗人IgG、游离阿霉素、小鼠抗人IgG-葡聚糖-阿霉素对S180细胞的毒性作用,比较阿霉素、小鼠抗人IgG-葡聚糖-阿霉素、小鼠抗人IgG-葡聚糖-阿霉素 人IgO的抑瘤作用及对荷瘤小鼠生存时间的影响.结果 制备的偶联物中,小鼠抗人IgG、葡聚糖与阿霉素物质的量比为1:2.5:38;偶联物保留了小鼠抗人IgG抗体活性;体外细胞毒性实验表明偶联物对S180细胞有体外杀伤作用.小鼠抗人IgG-葡聚糖-阿霉素 肿瘤中接种人IgG组对小鼠移植性S180肉瘤的抑瘤率达17.72%,与其他组比较有显著性差异.但并未延长荷瘤小鼠的生存时间.结论 通过在肿瘤组织中接种IgG非特异性靶点,用抗人IgG单克隆免疫靶向阿霉素治疗小鼠S180肉瘤较对照组具有靶向作用.

Anti-human IgG-dextran-adriamycin conjugate for immunotargeting of S180 sarcoma:effects on the tumor weight and survival time of the tumor-bearing mice

OBJECTIVE: To prepare anti-human IgG-dextran-adriamycin conjugate for immunotargeting of S180 sarcoma and assess its effects on the tumor weight and survival time of the tumor-bearing mice. METHODS: Anti-human IgG-dextran- adriamycin was synthesized by conjugating dextran and adriamycin with anti-human IgG. The immunoactivity of anti-human IgG-dextran-adriamycin was measured by enzyme-linked immunosorbent assay (ELISA), and the cytotoxicity of anti-human IgG, adriamycin, and the IgG-dextran-adriamycin conjugate against the tumor cells in vitro was evaluated using MTT assay. In mice bearing S180 sarcoma, the agents were tested for their effects against tumor cell growth and the survival time of mice. RESULTS: The molar ratio of anti-mouse IgG, dextran, and adriamycin was 1:2.5:38 in the conjugate. The conjugates were shown to retain the immunoactivity of anti-human IgG, and possessed cytotoxicity to S180 cells in vitro. Administration of the conjugate and intratumor injection of human IgG resulted in a tumor suppression rate of 17.72%in mice bearing S180 sarcoma, but did not prolong the survival time of the mice. CONCLUSION: The anti-human IgG-dextran-adriamycin conjugate shows targeted antitumor effect against S180 sarcoma in mice.