Anti-tumor immunity elicited by direct intratumoral administration of a recombinant adenovirus expressing either IL-28A/IFN-λ2 or IL-29/IFN-λ1
Anti-tumor immunity elicited by direct intratumoral administration of a recombinant adenovirus expressing either IL-28A/IFN-λ2 or IL-29/IFN-λ1
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DOI：
10.1038/cgt.2016.29
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发表时间：
2016-08-01
影响因子：
6.4
通讯作者：
Numasaki, M.
中科院分区：
文献类型：
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作者：
Hasegawa, K.;Tagawa, M.;Numasaki, M.
白介素28A/干扰素-lambda 2和IL-29/干扰素-lambda 1具有直接和间接的抗肿瘤作用。本研究构建了表达IL-28A/IFN-lambda 2(ADIL-28A)或IL-29/IFN-lambda 1(ADIL-29)的重组腺病毒载体，以评价重组腺病毒瘤内注射的治疗特性，应用于肿瘤基因治疗的临床应用。尽管对MCA205和B16-F10细胞缺乏抗增殖作用，但与AdNull相比，多次注射ADIL-28A或ADIL-429可延缓已建立的皮下肿瘤的生长。体内细胞耗竭实验表明，NK细胞和CD8(+)T细胞在ADIL-28A介导的肿瘤生长抑制中起主要作用。经ADIL-28A或ADIL-29处理后，肿瘤组织中CD8(+)T细胞的数量显著增加。此外，在用ADIL-28A或ADIL-29处理的动物的脾细胞中检测到了特异性的抗肿瘤细胞毒性T淋巴细胞反应。在干扰素-γ缺陷小鼠中，ADIL-28A的抗肿瘤活性完全受损，表明干扰素-γ在ADIL-28A引发的肿瘤生长抑制中起重要作用。IL-12与ADIL-28A联合应用具有协同抗肿瘤作用。这些结果表明，ADIL-28A和ADIL-29可以成功地作为一种替代的肿瘤免疫基因治疗。
Interleukin (IL)-28A/inteiferon (IFN)-lambda 2 and IL-29/IFN-lambda 1 have been demonstrated to elicit direct and indirect anti-tumor actions. In this study, We constructed an adenovirus vector expressing either IL-28A/IFN-lambda 2 (AdIL-28A) or IL-29/IFN-lambda 1 (AdIL-29) to evaluate the therapeutic properties of intraturnoral injection of recombinant adenovirus to apply for the clinical implementation of cancer gene therapy. Despite the lack of an anti-proliferative effect on MCA205 and B16-F10 cells, a retarded growth of established subcutaneous tumors was observed following multiple injections Of either AdIL-28A or AdIL-429 when compared with AdNull. In vivo cell depletion experiments displayed that both NK cells and CD8(+) T cells have a major role in AdIL-28A-mediated tumor growth suppression. A significant increase in the number of infiltrating CD8(+) T cells into the tumors-treated with either AdIL-28A or AdIL-29 was observed. Moreover, specific ant-Rumor cytotoxic T lymphocyte reactivity was detected in spleen cells from animals treated with either AdIL-28A or AdIL-29. In IFN-gamma-deficient mice, anti-tumor activities of AdIL-28A were completely impaired, indicating that IFN-gamma is critically involved in the tumor growth inhibition triggered by AdIL-28A. IL-12 provided a synergiostic anti-tumor effect when combined with AdIL-28A. These results indicate that AdIL-28A and AdIL-29 could be successfully utilized as an alternative cancer immunogene therapy.