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腺病毒介导的B7.1基因转移在小鼠脑肿瘤中诱导免疫抗肿瘤效应。

Adenovirus-mediated gene transfer of B7.1 induces immunological anti-tumor effects in a murine brain tumor.

作者信息

Morioka Jun, Kajiwara Koji, Yoshikawa Koichi, Ideguchi Makoto, Uchida Tetsuya, Ohmoto Yoshinori, Suzuki Michiyasu

机构信息

Department of Neurosurgery, Yamaguchi University School of Medicine, Japan.

出版信息

J Neurooncol. 2002 Oct;60(1):13-23. doi: 10.1023/a:1020260822669.

DOI:10.1023/a:1020260822669
PMID:12416541
Abstract

The purpose of the present study was to determine if adenovirus-mediated transfection of a syngeneic mouse brain tumor with the gene encoding B7.1 enhances immunogenicity against tumor. Malignant astrocytoma cells were transfected with adenoviral vectors carrying the B7.1 gene (AdB7). Immunocytochemical analysis confirmed the expression of B7.1 in vitro and in vivo. To investigate the effects of B7.1 expression on tumorigenicity of the malignant astrocytoma, mice were implanted intracerebrally with B7.1-transfected glioma cells. There was no significant difference in proliferation between B7.1-transfected cells and controls in vitro. Nevertheless, mice implanted with B7. 1-transfected cells survived significantly longer than those in the control groups. Immunocytochemical analysis of the tumors showed that there was infiltration of a number of CD8+ T-cells and CD25+ activated T-cells in the brain implanted with B7.1-transfected glioma cells. The results showed the possibility that adenovirus-mediated B7.1 gene transfection to a brain tumor induced activation of CD8+ cytotoxic T-lymphocytes.

摘要

本研究的目的是确定腺病毒介导的将编码B7.1的基因转染至同基因小鼠脑肿瘤中是否能增强抗肿瘤免疫原性。用携带B7.1基因的腺病毒载体(AdB7)转染恶性星形细胞瘤细胞。免疫细胞化学分析证实了B7.1在体内外的表达。为了研究B7.1表达对恶性星形细胞瘤致瘤性的影响,将转染了B7.1的胶质瘤细胞脑内植入小鼠。在体外,B7.1转染细胞与对照细胞之间的增殖没有显著差异。然而,植入转染了B7.1细胞的小鼠存活时间明显长于对照组。对肿瘤的免疫细胞化学分析表明,在植入转染了B7.1的胶质瘤细胞的脑内有大量CD8 + T细胞和CD25 + 活化T细胞浸润。结果表明腺病毒介导的B7.1基因转染脑肿瘤有诱导CD8 + 细胞毒性T淋巴细胞活化的可能性。

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本文引用的文献

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lacZ-neoR transfected glioma cells in syngeneic rats: growth pattern and characterization of the host immune response against cells transplanted inside and outside the CNS.同基因大鼠中经乳糖操纵子β-半乳糖苷酶-新霉素抗性基因(lacZ-neoR)转染的胶质瘤细胞:宿主对中枢神经系统内外移植细胞的免疫反应的生长模式及特征
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Apoptotic elimination of peripheral T lymphocytes in patients with primary intracranial tumors.原发性颅内肿瘤患者外周血T淋巴细胞的凋亡清除
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Induction of effective antitumor immunity in a mouse brain tumor model using B7-1 (CD80) and intercellular adhesive molecule 1 (ICAM-1; CD54) transfection and recombinant interleukin 12.
联合细胞毒性和免疫介导的基因疗法治疗脑肿瘤。
Curr Top Med Chem. 2005;5(12):1151-70. doi: 10.2174/156802605774370856.
利用B7-1(CD80)和细胞间黏附分子1(ICAM-1;CD54)转染及重组白细胞介素12在小鼠脑肿瘤模型中诱导有效的抗肿瘤免疫。
Int J Cancer. 1999 Aug 27;82(5):714-20. doi: 10.1002/(sici)1097-0215(19990827)82:5<714::aid-ijc15>3.0.co;2-q.
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Human glioma-induced immunosuppression involves soluble factor(s) that alters monocyte cytokine profile and surface markers.人类胶质瘤诱导的免疫抑制涉及可改变单核细胞细胞因子谱和表面标志物的可溶性因子。
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Adenoviral transduction of melanoma cells with B7-1: antitumor immunity and immunosuppressive factors.用B7-1对黑色素瘤细胞进行腺病毒转导:抗肿瘤免疫和免疫抑制因子
Cancer Immunol Immunother. 1998 Jul;46(5):283-92. doi: 10.1007/s002620050489.
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Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma.在实验性乳腺癌中使用γ干扰素和B7表达的组合增强抗肿瘤免疫反应。
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A double recombinant adenovirus expressing the costimulatory molecule B7-1 (murine) and human IL-2 induces complete tumor regression in a murine breast adenocarcinoma model.一种表达共刺激分子B7-1(小鼠)和人白细胞介素-2的双重组腺病毒在小鼠乳腺腺癌模型中诱导肿瘤完全消退。
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Gene therapy with modified tumor cells enables T-cell activation by stimulating pathways required for signal transduction.用修饰后的肿瘤细胞进行基因治疗可通过刺激信号转导所需的途径来激活T细胞。
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