Combination of interleukin 12 and interferon alpha gene therapy induces a synergistic antitumor response against colon and renal cell carcinoma.
Combination of interleukin 12 and interferon alpha gene therapy induces a synergistic antitumor response against colon and renal cell carcinoma.
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白细胞介素 12 和干扰素 α 基因疗法的组合可诱导针对结肠癌和肾细胞癌的协同抗肿瘤反应。
DOI：
10.1089/10430340050129477
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发表时间：
2000
影响因子：
4.2
通讯作者：
F. Pericle
中科院分区：
文献类型：
--
作者：
S. K. Mendiratta;A. Quezada;M. Matar;N. M. Thull;J. Bishop;J. Nordstrom;F. Pericle
本研究采用小鼠肾癌和结肠癌模型Renca和CT 26，研究了IL-12基因治疗联合IFN-α基因治疗的抗肿瘤效果和作用机制。用单独的鼠IL-12质粒或与用聚合物相互作用非缩合（PINC）基因递送系统配制的IFN-α质粒组合治疗肿瘤。单独瘤内注射IL-12 DNA/聚乙烯吡咯烷酮（PVP）分别诱导了58%和17%的Renca和CT 26肿瘤的排斥反应，而在IFN-α质粒/PVP治疗的小鼠中观察到25%（Renca）和0%（CT 26）的排斥反应。配制的质粒IL-12与IFN-α的组合基因疗法协同增加了对Renca（100%肿瘤排斥）和CT 26（50%）的抗肿瘤应答。体内白细胞亚群的清除表明，CD 8（+）T细胞和NK细胞是联合细胞因子基因治疗诱导的抗肿瘤反应的主要效应者。此外，在用IL-12和IFN-α质粒制剂联合治疗后排斥原发性肿瘤的小鼠产生了针对随后的肿瘤攻击的保护性免疫。对IL-12和IFN-α联合基因治疗小鼠肿瘤浸润性白细胞的分析显示，抗原呈递细胞（Mac-1（hi）细胞）上的CD 40分子上调。最后，趋化因子IP-10和TCA-3的mRNA水平在用细胞因子质粒的组合处理的肿瘤中高于用任一细胞因子基因单独处理的肿瘤。这些数据提供了证据表明，IL 12基因疗法与IFN-α基因疗法联合协同诱导已建立的肿瘤消退，并可能代表癌症治疗的新治疗策略。
The antitumor effect and mechanism of action of IL-12 gene therapy combined with IFN-alpha gene therapy were investigated in tumor-bearing mice using renal and colon carcinoma models, Renca and CT26, respectively. Tumors were treated with murine IL-12 plasmid alone or in combination with IFN-alpha plasmid formulated with a polymeric interactive noncondensing (PINC) gene delivery system. Intratumoral injection of IL-12 DNA/polyvinyl pyrrolidone (PVP) alone induced rejection of 58 and 17% of Renca and CT26 tumors, respectively, whereas 25% (Renca) and 0% (CT26) rejection was observed in mice treated with IFN-alpha plasmid/PVP. Combination gene therapy of formulated plasmids, IL-12 with IFN-alpha, synergistically increased the antitumor response against Renca (100% tumor rejection) and CT26 (50%). In vivo depletion of leukocyte subsets indicated that CD8(+) T and NK cells were the primary effectors of the antitumor response induced by the combined cytokine gene therapy. Moreover, mice that rejected the primary tumors after combined treatment with IL-12 and IFN-alpha plasmid formulation developed protective immunity against a subsequent tumor challenge. Analysis of tumor-infiltrating leukocytes from mice treated with the combined IL-12 and IFN-alpha gene therapy showed upregulation of CD40 molecules on antigen-presenting cells (Mac-1(hi) cells). Finally, levels of mRNA for the chemokines IP-10 and TCA-3 were higher in tumors treated with the combination of cytokine plasmids than in tumors treated with either cytokine gene alone. These data provide evidence that IL12 gene therapy combined with IFN-alpha gene therapy synergistically induces regression of established tumors and may represent a novel therapeutic strategy for cancer treatment.
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影响因子：
4.4
作者：
C. Tannenbaum;Nancy L. Wicker;D. Armstrong;R. Tubbs;J. Finke;R. Bukowski;T. Hamilton
通讯作者：
C. Tannenbaum;Nancy L. Wicker;D. Armstrong;R. Tubbs;J. Finke;R. Bukowski;T. Hamilton
影响因子：
4.4
作者：
H. Doyle;J. Murphy
通讯作者：
H. Doyle;J. Murphy
影响因子：
4.4
作者：
R. Stout;J. Suttles;Jianchao Xu;I. Grewal;R. Flavell
通讯作者：
R. Stout;J. Suttles;Jianchao Xu;I. Grewal;R. Flavell
影响因子：
56.9
作者：
HSIEH, CS;MACATONIA, SE;MURPHY, KM
通讯作者：
MURPHY, KM