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IL-23 gene therapy for mouse bladder tumour cell lines.

机译:IL-23基因疗法用于小鼠膀胱肿瘤细胞系。

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OBJECTIVES: * 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 MATERIALS AND METHODS: * 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. RESULTS: * 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. CONCLUSIONS: * 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.
机译:目的:*评估IL-23基因转移到小鼠膀胱癌(MBT2)细胞中的抗肿瘤作用。 *研究MBT2细胞随后构成IL-23的基本机制材料和方法:*通过脂质体介导的基因转移,将包含IL-23基因的表达载体导入MBT2细胞,并分泌IL-23。通过ELISA确认。 *将IL-23分泌的MBT2细胞(MBT2 / IL-23)的体内抗肿瘤作用是通过将细胞注射到同基因C3H小鼠中来检查的。 *进行了使用丝裂霉素C(MMC)处理的分泌IL-23的MBT2细胞进行的肿瘤疫苗接种研究,并且还研究了体内CD25耗竭对其他疫苗效果的有用性。 *通过CD8或CD4 T细胞或自然杀伤细胞的抗体消耗研究了抗肿瘤作用的潜在机制,并使用免疫组织化学评估了体内浸润肿瘤部位的细胞。结果:*用MBT2 / IL-23转导的稳定转化子将IL-23分泌到培养上清液中。 *基因工程分泌IL-23的MBT2细胞在同系小鼠中被排斥。 *接种了MBT2 / IL-23的小鼠抑制了在远处注射的亲代MBT2细胞的肿瘤生长,并且通过结合抗体体内的CD25消耗而增强了这种疫苗效果。 * MBT2 / IL-23具有直接抗肿瘤作用的主要效应细胞是CD8 T细胞,这在体内耗竭和免疫组织化学研究中显示。结论:* IL-23分泌的MBT2细胞被CD8 T细胞活化排斥在同系小鼠中。 * MMC处理的MBT2 / IL-23对亲代MBT2细胞具有肿瘤疫苗作用,并且通过与体内CD25耗竭相结合而增强了这种作用。

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