Electrotransfer of single-stranded or double-stranded DNA induces complete regression of palpable B16.F10 mouse melanomas
Electrotransfer of single-stranded or double-stranded DNA induces complete regression of palpable B16.F10 mouse melanomas
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DOI：
10.1038/cgt.2013.71
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发表时间：
2013-12-01
影响因子：
6.4
通讯作者：
Cemazar, M.
中科院分区：
文献类型：
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作者：
Heller, L.;Todorovic, V.;Cemazar, M.
在许多临床前模型中，电脉冲增强了质粒DNA在体内的肿瘤传递。肿瘤内电转移编码治疗分子的质粒已进入II期临床试验。在多个临床前研究中，在进行载体或主干质粒DNA电转移的对照组中，观察到肿瘤生长减少，存活率增加或肿瘤完全消退。本研究探讨了可能产生这种抗肿瘤作用的因素。采用特定的电转移脉冲协议显著增强了回归。在免疫正常和免疫缺陷小鼠中，在传递带有或不带有CpG基序的单链或双链DNA后，观察到肿瘤消退，表明先天免疫系统参与了对DNA的反应。总之，本研究表明，观察到的抗肿瘤作用不是单一因素所致，而是多种因素共同作用的结果。
Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of single-stranded or double-stranded DNA with or without CpG motifs in both immunocompetent and immunodeficient mice, indicating the involvement of the innate immune system in response to DNA. In conclusion, this study demonstrated that the observed antitumor effects are not due to a single factor, but to a combination of factors.