Mizuno M, Yoshida J
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
Cancer Immunol Immunother. 1998 Dec;47(4):227-32. doi: 10.1007/s002620050525.
We investigated the immunological responses induced by human interferon beta (IFNbeta) gene transfer in human gliomas produced in the brains of nude mice. A suspension of human glioma U251-SP cells was injected into the brains of nude mice. The IFNbeta gene was transferred by intratumoral injection with cationic liposomes or cationic liposomes associated with anti-glioma monoclonal antibody (immunoliposomes). When intratumoral injection of liposomes or immunoliposomes containing the human IFNbeta gene was performed every second day for a total of six injections, starting 7 days after tumor transplantation, complete disappearance of the tumor was observed in six of seven mice that had received liposomes and in all seven mice receiving immunoliposomes. In addition, experimental gliomas injected with immunoliposomes were much smaller than those injected with ordinary liposomes following delayed injections beginning 14 days after transplantation. An immunohistochemical study of the treated nude mouse brains revealed a remarkable induction of natural killer (NK) cells expressing asialoGM1 antigen. To investigate the significance of NK cells in the antitumor effect, we injected liposomes or immunoliposomes containing the human IFNbeta gene into tumors in nude mice depleted of NK cells by irradiation and anti-asialoGM1 antibody administration. The antitumor effect of the liposomes or immunoliposomes was abolished. Subsequent subcutaneous glioma challenge of the nude mice after intracerebral tumor implantation and gene transfer resulted in no subcutaneous tumor growth. These results suggest that the induction of NK cells is important in the cytocidal effect of liposomes or immunoliposomes containing the human IFNbeta gene upon experimental gliomas.
我们研究了人β干扰素（IFNβ）基因转移对裸鼠脑内产生的人胶质瘤所诱导的免疫反应。将人胶质瘤U251-SP细胞悬液注射到裸鼠脑内。通过肿瘤内注射阳离子脂质体或与抗胶质瘤单克隆抗体相关的阳离子脂质体（免疫脂质体）来转移IFNβ基因。当在肿瘤移植7天后开始每隔一天进行一次肿瘤内注射含有人IFNβ基因的脂质体或免疫脂质体，共注射6次时，在接受脂质体的7只小鼠中有6只以及接受免疫脂质体的所有7只小鼠中均观察到肿瘤完全消失。此外，在移植14天后开始延迟注射后，注射免疫脂质体的实验性胶质瘤比注射普通脂质体的胶质瘤小得多。对经治疗的裸鼠脑进行免疫组织化学研究显示，表达去唾液酸GM1抗原的自然杀伤（NK）细胞有显著诱导。为了研究NK细胞在抗肿瘤作用中的意义，我们将含有人IFNβ基因的脂质体或免疫脂质体注射到通过照射和给予抗去唾液酸GM1抗体而耗尽NK细胞的裸鼠肿瘤中。脂质体或免疫脂质体的抗肿瘤作用消失。在脑内肿瘤植入和基因转移后对裸鼠进行随后的皮下胶质瘤攻击，未出现皮下肿瘤生长。这些结果表明，NK细胞的诱导在含有人IFNβ基因的脂质体或免疫脂质体对实验性胶质瘤的杀伤作用中很重要。
