Department of Urology, Wakayama Medical University, Wakayama, Japan.
BJU Int. 2011 Sep;108(6):914-21. doi: 10.1111/j.1464-410X.2010.10025.x. Epub 2011 Mar 24.
• To evaluate the antitumour effects of IL-23 gene transfer into mouse bladder carcinoma (MBT2) cells. • To investigate the mechanisms underlying the subsequent constitutive secrection of IL-23 by the MBT2 cells
• An expression vector containing IL-23 gene was introduced into MBT2 cells by liposome-mediated gene transfer, and secretion of IL-23 was confirmed by ELISA. • The in vivo antitumour effect of IL-23-secreting MBT2 cells (MBT2/IL-23) was examined by injecting the cells into syngeneic C3H mice. • A tumour vaccination study using mitomycin C (MMC)-treated IL-23-secreting MBT2 cells was carried out, and the usefulness of in vivo CD25 depletion for an additional vaccine effect was also investigated. • The mechanisms underlying the antitumour effects were investigated by antibody depletion of CD8 or CD4 T cells, or natural killer cells, and cells infiltrating the tumour sites in vivo were assessed using immunohistochemistry.
• Stable transformants transduced with MBT2/IL-23 secreted IL-23 into the culture supernatant. • Genetically engineered IL-23-secreting MBT2 cells were rejected in syngeneic mice. • MBT2/IL-23-vaccinated mice inhibited the tumour growth of parental MBT2 cells injected at a distant site and this vaccine effect was enhanced by combination with in vivo CD25 depletion by an antibody. • The main effector cells for the direct antitumour effect of MBT2/IL-23 were CD8 T cells, which was shown by in vivo depletion and immunohistochemical study.
• IL-23-secreting MBT2 cells were rejected in syngeneic mice by the activation of CD8 T cells. • MMC-treated MBT2/IL-23 can have a tumour vaccine effect for parental MBT2 cells, and this effect was enhanced by combination with in vivo CD25 depletion.
评估白细胞介素 23（IL-23）基因转染入小鼠膀胱癌（MBT2）细胞的抗肿瘤作用。
研究 MBT2 细胞持续分泌 IL-23 的机制。
通过脂质体介导的基因转移将含有 IL-23 基因的表达载体导入 MBT2 细胞，通过 ELISA 确认 IL-23 的分泌。
将分泌 IL-23 的 MBT2 细胞（MBT2/IL-23）注入同基因 C3H 小鼠，观察其体内抗肿瘤作用。
进行了用丝裂霉素 C（MMC）处理的分泌 IL-23 的 MBT2 细胞的肿瘤疫苗研究，并研究了体内 CD25 耗竭对额外疫苗效果的作用。
通过抗体耗竭 CD8 或 CD4 T 细胞或自然杀伤细胞，以及用免疫组织化学评估体内浸润肿瘤部位的细胞，研究抗肿瘤作用的机制。
稳定转染的 MBT2/IL-23 转化体在培养上清液中分泌 IL-23。
遗传工程 IL-23 分泌的 MBT2 细胞在同基因小鼠中被排斥。
MBT2/IL-23 疫苗接种的小鼠抑制了远处注射的亲本 MBT2 细胞的肿瘤生长，这种疫苗效果通过与体内 CD25 耗竭的抗体联合增强。
MBT2/IL-23 的直接抗肿瘤作用的主要效应细胞是 CD8 T 细胞，这通过体内耗竭和免疫组织化学研究得到证实。
通过 CD8 T 细胞的激活，IL-23 分泌的 MBT2 细胞在同基因小鼠中被排斥。
MMC 处理的 MBT2/IL-23 可对亲本 MBT2 细胞产生肿瘤疫苗作用，并且这种作用通过与体内 CD25 耗竭的联合增强。
