目的:研究低剂量环磷酸胺(Cy)联合MHC Ⅰ类限制性肿瘤抗原多肽Mutl致敏、白细胞介素2(IL-2)基因修饰的树突状细胞(DCs)对转移性肺癌小鼠的治疗作用及其免疫学机理.方法:制备小鼠骨髓来源的DCs,用转移性Lewis肺癌特异性多肽Mutl预激经IL-2基因修饰的DCs联合低剂量Cy治疗转移性肺癌小鼠.通过FACS分析其脾细胞内T淋巴细胞比例的变化,~51Cr释放法检测CTL和NK细胞杀伤活性.结果:肿瘤抗原多肽致敏、IL-2基因修饰的DCs与小剂量Cy联合后,能比单用DCs更有效地治疗转移性肺癌,小鼠脾细胞中CD8~+T细胞和NK1.1~+细胞明显比例升高,联合治疗组诱导出的CTL杀伤活性最高.结论:以肿瘤抗原多肽冲击致敏的IL-2基因修饰的DCs联合小剂量Cy能更有效地促进荷瘤宿主免疫应答,具有显著地体内抑制肺癌转移的效果.

Objective: To investigate the antitumor effects and the possible mechanisms of tumor antigen peptide-pulsed, IL-2 gene-modified dendritic cells (DCs) in combination with low-dose cyclophosphamide (Cy). Methods: Mutl is a MHC class I -restricted tumor antigen peptide of 3LL Lewis lung carcinoma. The mice bearing metastatic lung carcinoma were treated by vaccination with DCs transfected with IL-2 gene and pulsed with Mutl, then the survival period of mice were observed. The phenotypes of splenocytes were detected by FACS and the cytotoxicity of CTL and NK were assayed by 4h-51Cr release assay. Results: The combind treatment could inhibit pulmonary metastasis of tumor most significantly and increase the proportion of the CD8 T cells, NK1.1 cells in spleen mononuclear cells. The highest CTL cytotoxicity could be induced. Conclusion: Tumor antigen peptide-pulsed,IL-2 gene-modified DCs combined with low-dose Cy could induce antitumor immune response most potently and then inhibit tumor pulmonary metastasis most significantly.

R392.12

国家自然科学基金重点项目(39730420);国家杰出青年科学基金(39825123)资助