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2×104个3LL瘤细胞皮下注射C57BL/6（H-2-b）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，24 h后在浓度为100 nmol/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25 mg/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（70.0 vs 27.5 d）; 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2×10 4 3LL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。

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 line 3LL with adenovirus encoding GM-GSF. Mice model of Lewis lung carcinoma was established by subcutaneous injection of 2×104 3LL cells into C57BL/6（H-2b）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/GM-CSF after pacilitaxel chemotherapy was 41.35% on day 3. Meanwhile, the survival mice could resist the re-attack of 3LL cells (2×104). 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.

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)