低剂量环磷酰胺增强MHCⅠ类限制性肿瘤抗原多肽冲击致敏的树突状细胞的抗肿瘤转移效果

来源 :中国肿瘤生物治疗杂志 | 被引量 : 0次 | 上传用户:kinglesssss
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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 effect of low-dose cyclic phospho-amine (Cy) combined with MHC class I-restricted tumor antigen peptide Mutl sensitized and interleukin 2 (IL-2) gene-modified dendritic cells (DCs) on metastatic lung cancer in mice Therapeutic effect and its immunological mechanism. Methods: Preparation of mouse bone marrow-derived DCs, pretreatment of IL-2 gene-modified DCs with metastatic Lewis lung cancer-specific peptide Mutl, and low-dose Cy treatment of metastatic lung cancer mice. By FACS The proportion of T lymphocytes in the spleen cells was analyzed, and cytotoxicity of CTL and NK cells was measured by ~51Cr release assay. Results: Tumor antigen sensitized, IL-2 gene-modified DCs and low-dose Cy were more effective than single use. DCs can treat metastatic lung cancer more effectively. The percentage of CD8~+ T cells and NK1.1~+ cells in mouse spleen cells increased significantly, and the CTL killing activity induced by combined treatment group was the highest. Conclusion: The impact of tumor antigen polypeptide Sensitized IL-2 gene-modified DCs combined with low-dose Cy can more effectively promote the tumor-bearing host immune response and has a significant effect of inhibiting lung metastasis in vivo.
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