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1.
GM-CSF及B7-1基因修饰的肿瘤细胞疫苗抗肿瘤的研究 总被引:2,自引:0,他引:2
目的:研究GM-CSF及B7-1基因修饰的肿瘤细胞作为瘤苗的有效性。方法:我们将小鼠GM-CSF及CD80基因通过逆转录病毒载体分别导入EL-4淋巴瘤细胞中,进而研究了EL-4/GM-CSF及EL-4/B7-1在同系C57B习中的成瘤性及其诱导抗肿瘤免疫的效果。结果:转B7-1基因的肿瘤细胞诱发了CD80的高表达。转基因的肿瘤细胞在同源小鼠中的成瘤性下降,免疫原笥增强。在肿瘤生长的早期对实验性荷瘤 相似文献
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重组白介素6—假单胞菌外毒素融合蛋白(IL6—PE40)特异性杀伤高… 总被引:2,自引:0,他引:2
作者报道了重组IL6-PE40对电转人IL6受体基因所建立的LT12-IL6R^+和LT12-IL6R^-大鼠急性髓细胞白血病模型的细胞毒效应。IL60PE40在1~1000μg/L呈剂量依赖性抑制LT12-IL6R^+细胞的CFU-L集落形成及DNA合成,相反此浓度的IL6-PE40对LT12-IL6R^-细胞的CFU-L几乎无抑制效应。当浓度在250~1000ng/ml时,DNA合成的抑制率仅 相似文献
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小鼠红白血病细胞来源的树突状细胞对特异性CTL的体内外诱 … 总被引:1,自引:0,他引:1
目的 探讨白细胞介素-12(IL-12)诱导小鼠红白血病细胞产生的树突状细胞,对白血病特异性CTL细胞的诱导作用,及体内免疫后对抗肿瘤免疫应答的诱导效果。方法:采用4小时^51Cr释放法,检测CTL杀伤活性;观察小鼠红白细胞病细胞来源的树突状细胞体内免疫治疗后对肿瘤的抑制作用,采用了HE染色和电镜等技术,分析肿瘤组织的病理学变化。结果:IL-12诱导FBL-3细胞产生的DC,在体外可诱导出FBL- 相似文献
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目的:评价IL-4基因转染人胃癌细胞株分泌IL-4的可行性。方法:用脂质体转染法将IL-4基因转入SGC-7901人胃癌细胞株,并检测细胞分泌的IL-4和对LAK细胞杀伤肿瘤细胞作用的影响。结果:IL-4基因可以转染入人胃癌细胞,并表达有活性IL-4,基因转染可以明显增强IL-2激活的LAK细胞的肿瘤杀伤作用,用大剂量的γ射线照射后,转染细胞仍可以持续分泌IL-43~4周期。结论:IL-4基因转染不改变胃癌细胞的体外生长特性,但可以明显增强抗肿瘤免疫反应 相似文献
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转基因细胞SPC-A-1/IL-2的致突变性研究 * 总被引:1,自引:0,他引:1
目的:观察转基因细胞SPC-A-1/IL-2的致突变作用,为转基因肿瘤细胞作为瘤苗进行临床应用的安全性检测提供依据。方法:在人IL-2的cDNA与逆转录病毒载体pLXSN重组并完成PA317/pLIL-2SN包装体系的基础上,将IL-2基因导入人肺腺癌胸膜转移细胞系SPC-A-1中并得到IL-2基因的稳定表达,然后通过遗传毒理学实验技术对转基因细胞SPC-A-1/IL-2的DNA及培养上清液进行体内和体外的致突变性实验研究。结果:转基因细胞SPC-A-1/IL-2的DNA及培养上清液均未显出致突变作用。结论:转基因细胞SPC-A-1/IL-2作为瘤苗应用可初步视为是安全可靠的。 相似文献
6.
本文研究了IL-2,IL-4,IL-6基因转染后B16黑色素瘤细胞表面MHCI类抗原及ICAM-1的表达水平,并探讨了基估CTL诱导过程中的作用。结果表明,IL-2,IL-4,IL-6基因转染B16黑素瘤细胞表面MHCI类抗原及ICAM-1表达均高于野生型B16黑色素瘤细胞及转染对照质粒的B16黑色素瘤细胞。 相似文献
7.
目的:探索TNF-α基因能否成功导入耐药细胞并获得表达,发挥生物学效应。方法:以重组逆转录病毒为载体将TNF-α基因导入具有多药耐药(MDR)表型的人乳腺癌细胞系MCF7/ADR,经G418抗生筛选获4株阳性克隆。PCR、Elisa法鉴定并检测TNF-α基因的整合和表达。细胞计数法观察细胞生长速度的改变,流式细胞仪检测细胞周期变化。结果:4株阳性克隆整合了TNF-α基因并获得表达,分泌TNF-α量 相似文献
8.
白细胞介素18基因修饰的树突状细胞的表型分析及其免?… 总被引:4,自引:0,他引:4
目的:研究IL-18基因修饰后的树突状细胞(DC)的表型和功能的变化。方法;以含IL-18基因的重组腺病毒体外转染小鼠骨髓来源的DC,ELISA检测IL-18分泌水平,以RT-PCR检测IL-18mRNA表达,以FACS法分析其DC表型变化,采用(^3H)-TdR检测其MLR的变化。 相似文献
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ANTITUMOR IMMUNITY AND VACCINE EFFECT INDUCED BY IL—12 SYNERGIZES B7—1 GENE TRANSFECTED CELLS 总被引:3,自引:0,他引:3
Cytokines play an crucial role in the induction of antitumor immunity. It have been demonstrated that cytokines such as IL-2, IL-4, IL-12 could stimulate immunity response in many basic and clinical experiment[1-3]. Interleukin 12 (IL-12) is a heterodimeric cytokine which consists of p40 and p35 subunits. It stimulates the proliferation and activation of T lymphocyte and other killer cells and induces the production of IFN-g by these cells[4, 5]. IL-12 promotes T helper type 1 responses.… 相似文献
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Since 1990, gene transduced tumor vaccine has been studied. Many articles reported that tumor cells transduced with some cytokine or costimulatory molecule could induce system antitumor immunity[1,2] In this study, EL-4 lymphoma was transduced with recombinant retrovirus containing the murine GM-CSF gene and B7-1 gene, respectively. The effect of gene transduction on antitumor immunity was investigated.MATERIALS AND METHODSMice and Cell Lines Female C57BL/6 mice were bought from … 相似文献
13.
Hisao Fukumoto Makoto Nishio Kazuto Nishio Yuji Heike Hitoshi Arioka Hirokazu Kurokawa Tomoyuki Ishida Kazuya Fukuoka Taisuke Nomoto Yuichiro Ohe Nagahiro Saijo 《Cancer science》1997,88(5):501-505
To investigate the immunoregulatory effect of murine mterferon-γ-inducing factor (mIGIF), we transfected Lewis lung carcinoma (IXC) cells with a mammalian expression vector containing the mIGIF complementary DNA. The culture medium of the transfectant cells stimulated interferon-γ (IFN-γ) production by spleen cells in vitro in the presence of anti-CD3 antibody and markedly potentiated the effect of interleukin-12 (IL-12) on IFN-γ production by spleen cells. mIGIF transfectant cells showed reduction of tumorigenicity and induction of an in vivo immimo-protective effect against the parental LLC cells. To examine the combined effect of systemic administration of recomhinant IL-12 (rIL-12) and local mIGIF on the tumorigenicity, mice were challenged with LLC or transfectant cells on day 0, and the tumor-bearing mice were injected with 50 ng of rIL-12 intraperitoneally from day 7 to 11. Systemic rIL-12 showed an anti-tumor effect. However, mIGIF gene expression did not potentiate this effect of systemic rIL-12 in vivo. 相似文献
14.
Hidetoshi Sumimoto Kenzaburo Tani Yukoh Nakazaki Tsuyoshi Tanabe Hitoshi Hibino Hirofumi Hamada Miyuki Azuma Shigetaka Asano 《International journal of cancer. Journal international du cancer》1997,73(4):556-561
B7-1 (CD80) co-stimulatory molecule gene–transduced Lewis lung carcinoma (LLC) cells (LLC/B7 cells) resulted in remarkable loss of tumorigenicity in syngeneic C57BL/6 mice (87.5% rejection) compared to B7-negative, wild-type LLC (LLC/wt) cells (0% rejection). However, mice that had rejected LLC/B7 cells developed almost no systemic immunity protective against challenge with wild-type tumor cells after 4 weeks (11.8% rejection). Enhancement of MHC class I (H-2Kb) expression of LLC/B7 cells with in vitro interferon-γ treatment did not result in enhancement of protective immunity. In vivo depletion assay revealed that abrogation of tumorigenicity in LLC/B7 depended on CD8+ T cells but not on CD4+ T cells. However, vaccination of C57BL/6 mice with irradiated LLC cells transduced with GM-CSF (LLC/GM) led to the induction of potent, specific immunity against challenge with the LLC/wt cells after 2 weeks (80.8% rejection). Next, we established a double transfectant of LLC cells expressing both B7-1 and GM-CSF (LLC/GM + B7). The tumorigenicity of these clonal cells was also remarkably suppressed (90% rejection) to the same degree as LLC/B7, whereas that of LLC/GM was not suppressed (0% rejection). Interestingly, mice that had rejected LLC/GM+B7 cells developed enhanced protective immunity against challenge with LLC/wt cells after 4 weeks (55.6% rejection) compared to the results of LLC/B7 cells (11.8%). To evaluate whether co-expression of GM-CSF and B7-1 enabled the tumor cells to activate cytotoxic T cells more efficiently than B7-1 alone, we performed an in vitro killing assay. We found that immunization with LLC/GM+B7 cells resulted in a 3-fold stronger cytotoxic response than that with LLC/B7. Our data indicate that co-transfection of the B7-1 co-stimulatory molecule and GM-CSF genes may be more effective for the induction of stronger protective immunity in this experimental system. Int. J. Cancer 73:556–561, 1997. © 1997 Wiley-Liss, Inc. 相似文献
15.
目的研究GM-CSF基因修饰的肿瘤细胞作为瘤苗的可行性.方法通过逆转录病毒载体,将小鼠GM-CSF基因导入EL-4淋巴瘤细胞中,研究EL-4/GM-CSF在同系C57BL/6小鼠中的成瘤性及其诱导抗肿瘤免疫的效果.结果EL-4/GM-CSF细胞在小鼠中的成瘤性下降,50%小鼠无瘤生存.射线灭活的EL-4/GM-CSF瘤苗能有效地保护野生型肿瘤细胞的攻击,在肿瘤生长的早期对实验性荷瘤小鼠进行治疗,能延长荷瘤宿主的存活时间(33.1±1.8)与对照组EL-4/Wt(23.2±1.5天)比差异有显著性(P<0.01).基因修饰的瘤苗作用明显增强.结论GM-CSF基因修饰的肿瘤疫苗可诱导较强的抗肿瘤免疫反应,导致肿瘤的部分根除,本实验为基因修饰的肿瘤疫苗的临床应用提出了一定的实验依据. 相似文献
16.
Inhibitory effects of B cells on antitumor immunity 总被引:4,自引:0,他引:4
B-cell functions in antitumor immunity are not well understood. In this study, we evaluated the role of B cells in the development of antitumor immunity using Friend murine leukemia virus gag-expressing mouse EL-4 (EL-4 gag), D5 mouse melanoma, or MCA304 mouse sarcoma cells. To screen tumors for susceptibility to B-cell-deficient immune environments, spleen cells from naive C57BL/6 [wild-type (WT)] and B-cell knockout (BKO) mice were cultured with irradiated tumor cells in vitro. When cells were stimulated with EL-4 gag or D5 (but not MCA304 tumors), IFN-gamma production from CD8 T cells and natural killer cells was markedly decreased in WT compared with BKO cultures. IFN-gamma production was correlated with CD40 ligand expression on the tumor and inversely with interleukin-10 (IL-10) production by B cells. Sorted WT B cells produced more IL-10 than CD40 knockout (CD40KO) B cells when cocultured with EL-4 gag or D5 (but not MCA304). IFN-gamma production by BKO cells was reduced by the addition of sorted naive WT B cells (partially by CD40KO B cells) or recombinant mouse IL-10. In vivo tumor progression mirrored in vitro studies in that WT mice were unable to control tumor growth whereas EL-4 gag and D5 tumors (but not MCA304) were eliminated in BKO mice. Robust in vivo antitumor CTLs developed only in BKO tumor-challenged mice. Our studies provide the first mechanistic basis for the concept that B-cell depletion could therapeutically enhance antitumor immune responses to certain tumors by decreasing IL-10 production from B cells. 相似文献
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There are currently extensive studies relating to cancer vaccines using tumor cells engineered to express immunogenes and cancer gene therapy using adenovirus (AdV)-mediated gene transfer. In this study, a mouse tumor cell line, VKCK, was cotransfected with genes coding for tumor necrosis factor-alpha (TNF-alpha) and costimulatory B7-1 molecule to enhance immunogenicity. The transfectant cell line VKCK-TNF-alpha/B7-1 showed reduced tumorigenicity and tumor regression. Its inoculation further induced protective immunity; both CD4+ and CD8+ T cells were involved in the induction phase, whereas only CD8+ T cells mediated the effector phase. Susceptible mice bearing VKCK tumors developed a T helper type 2-dominant response, whereas resistant mice with VKCK-TNF-alpha/B7-1 tumor regression developed a T helper type 1-dominant response to VKCK, indicating that the tumor regression was related to a shift in the cytokine profile of the host from type 2 to type 1. Vaccination of VKCK-TNF-alpha/B7-1 cells inhibited tumor formation derived from a single dose of 3 x 10(6) VKCK cells and eradicated 3-day tumors but not 10-day tumors. AdV-mediated TNF-alpha gene transfer by intratumoral injection of AdV-TNF-alpha significantly inhibited tumor growth but failed to eradicate any well-established tumors. However, combinational immunotherapy with vaccination of VKCK-TNF-alpha/B7-1 cells and AdV-mediated TNF-alpha gene transfer not only significantly inhibited tumor growth but also eradicated 10-day VKCK tumors in three of eight mice. Therefore, the present study may be useful not only in understanding the mechanisms responsible for an efficient antitumoral immunity, but also in establishing a more effective immunotherapeutic approach for cancer patients. 相似文献
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Tumour cells engineered to secrete interleukin-15 augment anti-tumour immune responses in vivo. 总被引:2,自引:0,他引:2
S Hazama T Noma F Wang N Iizuka Y Ogura K Yoshimura E Inoguchi M Hakozaki K Hirose T Suzuki M Oka 《British journal of cancer》1999,80(9):1420-1426
We examined the effect of interleukin-15 (IL-15) gene transfer into tumour cells on the host's anti-tumour response. In BALB/c mice IL-15 producing Meth-A cells (Meth-A/IL-15) underwent complete rejection, in a response characterized by massive infiltration of CD4+ T-cells and neutrophils. In contrast, Meth-A cells transfected with vector alone (Meth-A/Neo) grew rapidly. Moreover, rechallenged parental cells also were rejected in association with CD8* T-cell infiltration. However, in nude mice there was no drastic difference between Meth-A/IL-15 and Meth-A/Neo cells. These results demonstrate that IL-15-secreting tumour cells can stimulate local and systemic T-cell-dependent immunity and therefore may have a potential role in cancer therapy. 相似文献
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The ability of interleukin 2 (IL-2) to enhance in vivo antitumor immunity has been evaluated in the line 1 alveolar cell carcinoma (L1) model of BALB/c mice. A crude supernatant from phorbol myristate acetate exposed EL-4 cells rich in IL-2 plus other lymphokines (EL-4 IL-2), a concanavalin A-induced supernatant from murine splenocytes (Con A IL-2), and recombinant IL-2 (rIL-2) provided by Biogen were tested. Mice were immunized with a cloned population of L1 cells (10(6) irradiated L1 cells given s.c. in the left inguinal region) followed by s.c. injections of EL-4 IL-2, Con A IL-2, or rIL-2 given to the same site. Two immunizations of L1 cells each followed by IL-2 administration were given prior to challenge with live L1 cells s.c. on the right chest wall. Mice receiving EL-4 IL-2 survived significantly longer than those receiving L1 cells only. Daily administration of EL-4 IL-2 for 7 days after the last L1 immunization was significantly better than 3 days (P less than 0.01) which in turn was significantly better than 1 day (P less than 0.05). Among the doses tested (normalized in vitro to the Biologic Response Modifiers Program IL-2 standard) 404 units of IL-2/injection was optimal. The EL-4 IL-2 had to be injected adjacent to the site of L1 cells; s.c. injection at a distant site or i.p. was not effective. When rIL-2 or Con A IL-2 was substituted for EL-4 IL-2, survival was not prolonged; however, if Con A IL-2 (low IL-2 levels) was supplemented with rIL-2 to 404 units of IL-2, it augmented immunity as well as 404 units of EL-4 IL-2. The data suggest that IL-2 is not the only lymphokine active in augmenting antitumor immunity induced by L1 cells. Some preliminary experiments indicate that a multilymphokine approach may have potential clinical relevance. 相似文献