紫杉醇与肿瘤疫苗联合应用对小鼠Lewis肺癌皮下移植瘤的治疗效果  

Efficacy of 3LL/GM-CSF tumor vaccine combined with pacilitaxel chemotherapy in treatment of mice bearing transplanted Lewis lung carcinoma

作　　者：郑秀娟[1] 张镭[1] 林怡[1] 张毅[1] 胡红明[1] 储以微[1] 

机构地区：[1]复旦大学上海医学院免疫学系,教育部分子医学重点实验室,上海200032

出　　处：《中国肿瘤生物治疗杂志》2006年第6期442-446,共5页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金资助项目(No.30571713);复旦大学上海医学院临床基础交叉基金资助项目(No.2005JL19)

摘　　要：目的评价化疗药物紫杉醇联合应用肿瘤疫苗对小鼠Lewis肺癌皮下移植瘤的治疗效果。方法以编码有GM-CSF的腺病毒感染Lewis肺癌细胞3LL,制备肿瘤疫苗3LL/GM-CSF。以2×104个3LL瘤细胞皮下注射C57BL/6(H-2b)小鼠腹股沟部,制备小鼠皮下移植瘤。检测体内、外应用紫杉醇对Lewis肺癌细胞3LL的杀伤敏感性。在小鼠Lewis肺癌皮下移植瘤体内首先以紫杉醇化疗,随后以肿瘤疫苗3LL/GM-CSF免疫;或反之,首先以肿瘤疫苗免疫,随后以紫杉醇化疗,观察肿瘤生长和小鼠生存状况,以及检测小鼠体内对肿瘤的特异性杀伤效率和免疫应答记忆反应。结果紫杉醇体外作用于3LL肿瘤细胞,24h后在浓度为100nmol/L时可使32.10%的3LL肿瘤细胞发生死亡;但体内注射紫杉醇(5、10和25mg/kg)不能使所有3LL荷瘤小鼠肿瘤消退。体内使用紫杉醇后应用3LL/GM-CSF肿瘤疫苗,70%的荷瘤小鼠发生显著的肿瘤消退,与单纯化疗的小鼠相比生存时间明显延长(70.0vs27.5d);化疗后应用肿瘤疫苗诱导了体内对3LL的特异性杀伤,第3天体内杀伤率达41.35%;同时,存活小鼠能抵抗2×1043LL肿瘤细胞的再次攻击。接种3LL/GM-CSF肿瘤疫苗后应用紫杉醇化疗却不能使肿瘤消退。结论化疗后应用肿瘤疫苗免疫可诱导出抗原特异性免疫效应,使荷瘤小鼠肿瘤消退并延长生存时间,为临床开展化疗后的肿瘤疫苗主动免疫提供了实验依据。Objective： To evaluate the efficacy of 3LL/GM-CSF tumor vaccine combined with pacilitaxel chemotherapy in treatment of mice bearing transplanted Lewis lung carcinoma. Methods： The tumor vaccine 3LL/GM-CSF was prepared by infecting Lewis lung carcinoma cell fine 3 LL with adenovirus encoding GM-GSF. Mice model of Lewis lung carcinoma was established by subcutaneous injection of 2 ×10^4 3LL cells into C57BL/6 （ H-2^b ） mice. The sensitivity of Lewis lung carcinoma cell line-3LL to the treatment of pacilitaxel was detected in vivo and in vitro. The mice tumor model was first treated with pacilitaxel chemotherapy and then with 3LL/GM-CSF, or first with 3LL/GM-CSF and then with pacilitaxel. Tumor growth and the long-term survival of mice were observed after treatment. The immune memory and cytotoxicity against target cells were studied in the mice. Results： Pacilitaxel at 100 nmol/L killed 32.10% 3LL cells after 24 hour in vitro; but pacilitaxel at 5-25 mg/kg only had a poor effect on growth of 3LL cells in vivo. The tumors rebated in 70% of mice treated with pacilitaxel chemotherapy and 3LL/GM-CSF vaccination successively, and the survival of these mice was obviously longer than that of pure pacilitaxel chemotherapy group （70.0 days vs 27.5 days）. The killing rate of 3LL/GMCSF after pacilitaxel chemotherapy was 41.35% on day 3. Meanwhile, the survival mice could resist the re-attack of 3LL cells （2 × 10^4）. We also noticed that first treatment with 3LL/GM-CSF and then pacilitaxel chemotherapy had no effect on tumors. Conclusion： Application of tumor vaccine shortly after pacilitaxel chemotherapy can induce specific immune responses and prolong the survival of experimental mice, which provide a basis for future clinical practice.

关 键 词：紫杉醇 肿瘤疫苗 3LL/GM—CSF 肿瘤免疫治疗 

分 类 号：R392.11[医药卫生—免疫学]