Induction of anti-tumor immunity by mouse tumor cells transfected with mouse interleukin-12 gene.

S Obana, H Miyazawa, E Hara, T Tamura, H Nariuchi, M Takata, S Fujimoto, H Yamamoto
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引用次数: 17

Abstract

Interleukin-12 (IL-12) is a heterodimeric cytokine. In order to transduce both cDNAs for p35 and p40 of IL-12 in the tumor cells, a polycistronic retroviral vector was constructed by inserting the internal ribosome entry site gene of encephalomyocarditis virus between two cDNAs. On the other hand, two cDNAs were sequentially transfected in the tumor cells. Both polycistronic gene transfectants and double transfectants produced biologically active mouse IL-12. IL-12-expressing tumor cells were all rejected in syngeneic mice, and induced cytotoxic T lymphocyte activity. The capacity to induce anti-tumor memory may depend on the amount of IL-12 produced by the transfectants, because the relatively higher IL-12 producer tumor cell line induced the anti-tumor memory in the rejected mice, but the lower producer did not.

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转染小鼠白细胞介素-12基因的小鼠肿瘤细胞诱导抗肿瘤免疫。
白细胞介素-12 (IL-12)是一种异二聚体细胞因子。为了在肿瘤细胞中转导IL-12的p35和p40 cdna,我们在两个cdna之间插入脑心肌炎病毒内核糖体进入位点基因,构建了多顺反转录病毒载体。另一方面,在肿瘤细胞中依次转染两种cdna。多顺反子基因转染和双基因转染均产生具有生物活性的小鼠IL-12。表达il -12的肿瘤细胞在同基因小鼠中均被排斥,并诱导细胞毒性T淋巴细胞活性。诱导抗肿瘤记忆的能力可能取决于转染物产生IL-12的量,因为相对较高IL-12产生率的肿瘤细胞系诱导了被排斥小鼠的抗肿瘤记忆,而较低IL-12产生率的肿瘤细胞系则没有。
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