Synergistic antitumor effects of interleukin-12 gene transfer and systemic administration of interleukin-18 in a mouse bladder cancer model
Synergistic antitumor effects of interleukin-12 gene transfer and systemic administration of interleukin-18 in a mouse bladder cancer model
复制标题
白细胞介素 12 基因转移和白细胞介素 18 全身给药在小鼠膀胱癌模型中的协同抗肿瘤作用
DOI：
--
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
S. Kamidono
中科院分区：
文献类型：
--
作者：
K. Yamanaka;I. Hara;H. Nagai;H. Miyake;K. Gohji;M. Micallef;M. Kurimoto;S. Arakawa;S. Kamidono
摘要我们将白细胞介素12(IL-12)基因导入小鼠膀胱癌细胞系(MBT2)，建立了分泌具有生物活性的IL-12亚系。将分泌IL-12的MBT2(MBT2/IL-12)亚系移植到具有免疫功能的C3H小鼠皮下，可被完全排斥。尽管将分泌IL-12的细胞注射到CD8+T或CD4+T细胞已被相应抗体耗尽的免疫缺陷小鼠体内时，这种抗肿瘤作用没有改变，但当自然杀伤细胞被抗asialoGM1抗体耗尽时，这种抗肿瘤作用就被取消了。此外，当亲本MBT2细胞与MBT2/IL-12细胞混合注射到小鼠皮下时，MBT2/IL-12混合细胞可抑制亲本肿瘤的生长。此外，全身应用IL-18可增强这种抗肿瘤作用。当干扰素-γ中和抗体在 体内处理小鼠时，这种协同作用被取消。总而言之，局部分泌的IL-12导致了有效的抗肿瘤活性，全身应用IL-18可以增强这种活性。干扰素-γ在IL-12基因转导和IL-18全身给药的协同作用中发挥重要作用。
Abstract We introduced the interleukin-12 (IL-12) gene into the mouse bladder cancer cell line (MBT2) to establish sublines that secrete bioactive IL-12. IL-12-secreting MBT2 (MBT2/IL-12) sublines were completely rejected when subcutaneously implanted into immunocompetent syngeneic C3H mice. Although this antitumor effect did not change when IL-12-secreting cells were injected into immunodeficient mice whose CD8+ T or CD4+ T cells had been depleted by the corresponding antibody, it was abrogated when natural killer cells were depleted by anti-asialoGM1 antibody. In addition, when parental MBT2 cells mixed with MBT2/IL-12 cells were subcutaneously injected into mice, admixed MBT2/IL-12 inhibited the growth of the parental tumor. Furthermore, this antitumor effect was enhanced by systemic IL-18 administration. This synergism was abrogated when the mice were treated with interferon-γ-neutralizing antibody in vivo. In conclusion, local secretion of IL-12 led to effective antitumor activity that was enhanced by systemic administration of IL-18. Interferon-γ plays an important role in the synergism of IL-12 gene transduction and systemic administration of IL-18.
一种 cDNA 克隆载体，允许在哺乳动物细胞中表达 cDNA 插入片段。
影响因子：
5.3
作者：
Okayama,H;Berg,P
通讯作者：
Berg,P
使用多顺反子逆转录病毒载体通过 IL-12 基因治疗有效根除已建立的小鼠肿瘤。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Tahara,H;Zitvogel,L;Storkus,WJ;Zeh3rd,HJ;McKinney,TG;Schreiber,RD;Gubler,U;Robbins,PD;Lotze,MT
通讯作者：
Lotze,MT