Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication
Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication
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DOI：
10.1089/10430340050016157
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发表时间：
2000-01-01
影响因子：
4.2
通讯作者：
Dubinett, SM
中科院分区：
文献类型：
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作者：
Miller, PW;Sharma, S;Dubinett, SM
在两个小鼠肺癌模型中，瘤内给予腺病毒白细胞介素7-transdnced树突状细胞（DC-AdIL-7），导致肿瘤完全消退。肿瘤内DC-AdIL-7治疗与用特异性肿瘤肽抗原脉冲的DC一样有效。与其他肿瘤内治疗（包括重组IL-7、单独的AdIL-7载体、未修饰的DC、IL-7转导的成纤维细胞或用肿瘤裂解物脉冲的DC）的比较显示DC-AdIL-7治疗在实现抗肿瘤应答和增强免疫原性方面具有上级优势，由于DC-AdIL-7或AdIL-7治疗而具有完全肿瘤根除的小鼠在完全肿瘤根除后30天或更长时间用亲本肿瘤细胞再激发。所有DC-AdIL-7治疗的小鼠完全拒绝二次再激发，而AdIL-7处理的小鼠仅在20-25%的小鼠中具有持续的抗肿瘤作用，DC-AdIL-7疗法在实现全身抗肿瘤应答和增强免疫原性方面比AdIL-7更有效。在完全肿瘤根除后，用DC-AdIL-7处理的那些小鼠证明脾细胞GM-CSF和IFN-γ的释放比对照或AdIL-7处理的小鼠显著更大。在肿瘤内注射后，基因修饰的DC从肿瘤运输到淋巴结部位和脾脏，在肿瘤内注射后长达7天在结组织中检测到DC，我们报告，肿瘤内DC-AdIL-7导致显着的全身免疫反应和有效的抗肿瘤作用，在小鼠肺癌模型。
In two murine lung cancer models adenoviral interleukin 7-transdnced dendritic cells (DC-AdIL-7) were administered intratumorally, resulting in complete tumor regression. Intratumoral DC-AdIL-7 therapy was as effective as DCs pulsed with specific tumor peptide antigens, Comparison with other intratumoral therapies including recombinant IL-7, AdIL-7 vector alone, unmodified DCs, IL-7-transduced fibroblasts, or DCs pulsed with tumor lysates revealed DC-AdIL-7 therapy to be superior in achieving antitumor responses and augmenting immunogenicity, Mice with complete tumor eradication as a result of either DC-AdIL-7 or AdIL-7 therapy were rechallenged with parental tumor cells 30 days or more after complete tumor eradication, All the DC-AdIL-7-treated mice completely rejected a secondary rechallenge, whereas the AdIL-7-treated mice had sustained antitumor effects in only 20-25% of the mice, DC-AdIL-7 therapy was more effective than AdIL-7 in achieving systemic antitumor responses and enhancing immunogenicity. After complete tumor eradication, those mice treated with DC-AdIL-7 evidenced significantly greater release of splenocyte GM-CSF and IFN-gamma than did controls or AdIL-7-treated mice, After intratumoral injection, gene-modified DCs trafficked from the tumor to lymph node sites and spleen, DCs were detected in nodal tissues for up to 7 days after intratumoral injection, We report that intratumoral DC-AdIL-7 leads to significant systemic immune responses and potent antitumor effects in murine lung cancer models.