A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon α

A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon α
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DOI:
10.1073/pnas.96.4.1553
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发表时间:
1999-02-16
影响因子:
11.1
通讯作者:
Parker, SE
Parker, SE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Horton, HM;Anderson, D;Parker, SE

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描述了一种癌症治疗,其中i.m.注射编码鼠干扰素α(mIFN-α)的质粒DNA(pDNA)对小鼠的原发性和转移性肿瘤产生有效的抗肿瘤作用。皮下注射B16 F10黑素瘤、Cloudman黑素瘤或神经胶质瘤261肿瘤的小鼠,在所有三种肿瘤模型中,在IFN pDNA治疗后发现肿瘤体积显著减小和存活率提高。mIFN-alpha pDNA可以每隔一周注射一次,并且仍然产生显著的抗肿瘤作用,并且在转移性肿瘤模型中,该治疗显著减少了肺肿瘤转移的数量。免疫细胞亚群的耗竭表明抗肿瘤反应需要CD 8(+)T细胞。这些研究表明,原发性和转移性肿瘤可以通过i.m.注射编码细胞因子基因的质粒。
A cancer treatment is described in which i.m. injection of plasmid DNA (pDNA) encoding murine interferon alpha (mIFN-alpha) leads to potent antitumor effects on primary and metastatic tumors in mice. Mice bearing s.c, B16F10 melanoma, Cloudman melanoma, or glioma 261 tumors were injected i.m.,vith mIFN-alpha pDNA, In all three tumor models, a significant reduction in tumor volume and enhancement of survival was found after IFN pDNA therapy. The mIFN-alpha pDNA could be injected as infrequently as once every other week and still produce a significant antitumor effect, and, in a metastatic tumor model, the therapy markedly reduced the number of lung tumor metastases. Depletion of immune cell subsets indicated that CD8(+) T cells were required for the antitumor response. These studies demonstrate that primary and metastatic tumors can be treated systemically by i.m. injection of a plasmid encoding a cytokine gene.