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Volume 3,Issue 2,1996 Table of Contents
JunkoAbe
,
YokoYoshida
,
SatoshiOkabe
,
HiroakiWakimoto
,
Masaruaoyagi
,
KimiyoshiHirakawa
,
HirofumiHamada
1996, 3(2):96-103.
DOI: 10.3872/j.issn.1007-385X.1996.2.003
Abstract:
In vivo effects of IL-10 on host antitumor immunity were tested in murine tumor models. Gene transduction of Colon 26 cells with murine IL-10 gene resulted in a marked decrease of tumorigenicity in vivo. A cell line of CD8-positive cytotoxic T lymphocytes (CD8 CTL) with strong cytolytic activity against Colon 26 wasestablished , and therapeutic effect of IL-10 gene introduction into the CD8 CTL was studied. A recombinant adenovirus Adexl CAmILl0 enabled us to achieve very efficient gene transduction and high level production of IL-10 in murine lymphocytes. IL-10 gene - transduction of CTL exerted an increased antitumor response in the adoptive treatment models, resulting in markedly reduced numbers of metastatic nodules in the lung. Our findings indicate that IL - 10 works as an immunostimulator in the adoptive transfer therapy with tumor - specific CTL.
In vivo effects of IL-10 on host antitumor immunity were tested in murine tumor models. Gene transduction of Colon 26 cells with murine IL-10 gene resulted in a marked decrease of tumorigenicity in vivo. A cell line of CD8-positive cytotoxic T lymphocytes (CD8 CTL) with strong cytolytic activity against Colon 26 wasestablished , and therapeutic effect of IL-10 gene introduction into the CD8 CTL was studied. A recombinant adenovirus Adexl CAmILl0 enabled us to achieve very efficient gene transduction and high level production of IL-10 in murine lymphocytes. IL-10 gene - transduction of CTL exerted an increased antitumor response in the adoptive treatment models, resulting in markedly reduced numbers of metastatic nodules in the lung. Our findings indicate that IL - 10 works as an immunostimulator in the adoptive transfer therapy with tumor - specific CTL.
1996, 3(2):104-107.
DOI: 10.3872/j.issn.1007-385X.1996.2.004
Abstract:
The results of the current studies demonstrated that the combined use of IL - 2 and IL - 7 could augment the in vitro proliferative responses of tumor - specific T cell lines and clones to antigen stimulation, increasing stimulation induces 6 to 8 times greater than using either IL - 2 or IL - 7 alone. Antigen - driven T cells maintained in culture using this combined cytokine regimen can be induced to grow and maintained functional in large numbers and survive long-term in cultrue with each antigen restimulation cycle prolonged to six weeks. The IL-2 doses used in this combined cytokine regimen can be reduced 10 to 100 times that of cultures using IL-2 alone. Thus, the combined use of IL-2 plus IL-7 is effective for procuring large numbers of antigen - specific functional T cells in vitro.
The results of the current studies demonstrated that the combined use of IL - 2 and IL - 7 could augment the in vitro proliferative responses of tumor - specific T cell lines and clones to antigen stimulation, increasing stimulation induces 6 to 8 times greater than using either IL - 2 or IL - 7 alone. Antigen - driven T cells maintained in culture using this combined cytokine regimen can be induced to grow and maintained functional in large numbers and survive long-term in cultrue with each antigen restimulation cycle prolonged to six weeks. The IL-2 doses used in this combined cytokine regimen can be reduced 10 to 100 times that of cultures using IL-2 alone. Thus, the combined use of IL-2 plus IL-7 is effective for procuring large numbers of antigen - specific functional T cells in vitro.
1996, 3(2):108-113.
DOI: 10.3872/j.issn.1007-385X.1996.2.005
Abstract:
粒细胞集落刺激因子(G-CSF)具有明显的促进粒系造血祖细胞分化成熟、有效地提高外周血白细胞数量的作用;体内单独应用还具有抑制肿瘤的生长、抗肿瘤转移的作用。为了探讨G-CSF基因治疗及其配合大剂量化疗后的体内抗肿瘤效果,我们以C-26结肠癌小鼠为模型,研究腹腔内移植成纤维细胞介导的G-CSF基因治疗,rhG-CSF直接注射治疗,以及分别配合化疗后对肿瘤的治疗作用。结果发现,rhG-CSF直接注射疗法可明显抑制早期结肠癌小鼠肿瘤的生长(P<0.01),明显延长早期荷瘤小鼠的存活期;G-CSF基因治疗可明显抑制早期、中期结肠癌小鼠肿瘤生长(P<0.01),明显延长早期、中期结肠癌小鼠的存活期(P<0.01)。配合大剂量化疗后,rhG-CSF注射疗法及G-CSF基因疗法可更明显地抑制结肠癌小鼠肿瘤的生长,更明显延长结肠癌小鼠的存活期。结果表明,G-CSF基因疗法可有效地延长结肠癌小鼠的存活期,配合大剂量化疗能更有效地发挥抗肿瘤作用,提高结肠癌小鼠的存活期;同时表明,G-CSF基因治疗具有比应用rhG-CSF更显著的体内抑制肿瘤的效果。
粒细胞集落刺激因子(G-CSF)具有明显的促进粒系造血祖细胞分化成熟、有效地提高外周血白细胞数量的作用;体内单独应用还具有抑制肿瘤的生长、抗肿瘤转移的作用。为了探讨G-CSF基因治疗及其配合大剂量化疗后的体内抗肿瘤效果,我们以C-26结肠癌小鼠为模型,研究腹腔内移植成纤维细胞介导的G-CSF基因治疗,rhG-CSF直接注射治疗,以及分别配合化疗后对肿瘤的治疗作用。结果发现,rhG-CSF直接注射疗法可明显抑制早期结肠癌小鼠肿瘤的生长(P<0.01),明显延长早期荷瘤小鼠的存活期;G-CSF基因治疗可明显抑制早期、中期结肠癌小鼠肿瘤生长(P<0.01),明显延长早期、中期结肠癌小鼠的存活期(P<0.01)。配合大剂量化疗后,rhG-CSF注射疗法及G-CSF基因疗法可更明显地抑制结肠癌小鼠肿瘤的生长,更明显延长结肠癌小鼠的存活期。结果表明,G-CSF基因疗法可有效地延长结肠癌小鼠的存活期,配合大剂量化疗能更有效地发挥抗肿瘤作用,提高结肠癌小鼠的存活期;同时表明,G-CSF基因治疗具有比应用rhG-CSF更显著的体内抑制肿瘤的效果。
1996, 3(2):120-123.
DOI: 10.3872/j.issn.1007-385X.1996.2.007
Abstract:
This is the first report on gene therapy of mice melanoma by HSV - tk/ACV system. The sensitivity to ACV of genetically modified B16 cells (B16LNTK) was much higher than that of the parental cells. The sensitivity to ACV of B16 cells was increased when they were co - cultured with B16LNTK cells with various ratios. which showed the exist of the by stander effects. The tumor volume of B16LNTK (0.25cm3) is 94% less than that of B16 in C57BL/6 mice after 20-days ACV treatment. (P< 0.01) . B16 tumor loaded mice were treated in situ with HSV-tk /ACV, a significant effect was obtained. The tumor volume of B16 decreased to 57% of its origin. (P < 0. 05) The above results showed the HSV - tk/ACV system is a promising method for gene therapy of mice melanoma.
This is the first report on gene therapy of mice melanoma by HSV - tk/ACV system. The sensitivity to ACV of genetically modified B16 cells (B16LNTK) was much higher than that of the parental cells. The sensitivity to ACV of B16 cells was increased when they were co - cultured with B16LNTK cells with various ratios. which showed the exist of the by stander effects. The tumor volume of B16LNTK (0.25cm3) is 94% less than that of B16 in C57BL/6 mice after 20-days ACV treatment. (P< 0.01) . B16 tumor loaded mice were treated in situ with HSV-tk /ACV, a significant effect was obtained. The tumor volume of B16 decreased to 57% of its origin. (P < 0. 05) The above results showed the HSV - tk/ACV system is a promising method for gene therapy of mice melanoma.
Wang Luqun
,
Chi Cuifang
,
Kong Fansheng
,
Huang Ning
,
Liu Ximin
,
Li Mei
,
Zhang Donghong
,
Zhou Yuelan
,
Zhang Minghong
,
Song Suqin
1996, 3(2):124-126.
DOI: 10.3872/j.issn.1007-385X.1996.2.008
Abstract:
Ten patients with myelodysplastic syndrome (MDS) were treated with monoclonal anti -human T lymphocyte antibodies SMU3 (anti - CD3) and SMU8 (anti - CD8) . The results suggested that two patients got a significant progress and five patients turned better. Before treatment the patients had less CD4 cells, more CD8 cells, lower or inverted ratio of CD4/ CD8, higher expression of HLA -DR antigen than normal control and these differences were significant. After treatment T lymphocyte subsets and HLA - DR expression turned normal. T lymphocyte subsets imbalance and abnormal function in patients is one of the factors which induced MDS.
Ten patients with myelodysplastic syndrome (MDS) were treated with monoclonal anti -human T lymphocyte antibodies SMU3 (anti - CD3) and SMU8 (anti - CD8) . The results suggested that two patients got a significant progress and five patients turned better. Before treatment the patients had less CD4 cells, more CD8 cells, lower or inverted ratio of CD4/ CD8, higher expression of HLA -DR antigen than normal control and these differences were significant. After treatment T lymphocyte subsets and HLA - DR expression turned normal. T lymphocyte subsets imbalance and abnormal function in patients is one of the factors which induced MDS.
1996, 3(2):127-129.
DOI: 10.3872/j.issn.1007-385X.1996.2.009
Abstract:
Sixty - eight cancer patients were treated with tumor infiltrating lymphocytes transferred by local injection (local group) , in vein injecition (vein group) and in vein local injection (vein local group) respectively. We have analysed the anticancer efficacy and one year survival rate of patients with different transfer ways. It showed that the anticancer efficacy of the local group (85. 7%) was higher than that of vein group (48. 6%), but the one year survival rate of local group (66%) was lower than that of the vein group (80%). Comparative studies on circulating lymphocytes of cancer patients demonstrated that the increase of CD3 , CD8 , CD4 T lymphocytes of vein group were higer than that of local group, but not different from that of vein local group. These results suggest the possibility that in vein transfer of TILs could induce immuno -activation of cellular immunity to enhance the one year survial rate.
Sixty - eight cancer patients were treated with tumor infiltrating lymphocytes transferred by local injection (local group) , in vein injecition (vein group) and in vein local injection (vein local group) respectively. We have analysed the anticancer efficacy and one year survival rate of patients with different transfer ways. It showed that the anticancer efficacy of the local group (85. 7%) was higher than that of vein group (48. 6%), but the one year survival rate of local group (66%) was lower than that of the vein group (80%). Comparative studies on circulating lymphocytes of cancer patients demonstrated that the increase of CD3 , CD8 , CD4 T lymphocytes of vein group were higer than that of local group, but not different from that of vein local group. These results suggest the possibility that in vein transfer of TILs could induce immuno -activation of cellular immunity to enhance the one year survial rate.
1996, 3(2):135-139.
DOI: 10.3872/j.issn.1007-385X.1996.2.011
Abstract:
为提高IL-6在真核系统中的表达效率,我们在构建真核表达载体pcDNA3IL-6的基础上,用表达载体pCI中的CMV启动子和下游所带的β-球蛋白的第一个内含子,置换了pcDNA3中的CMV启动子,构建了一种新的表达载体,使IL-6的表达水平提高了7.5倍。此外,我们还研究了pAdVAntage共转染对IL-6表达的影响,使之表达水平提高了3.6倍。以上结果为细胞因子在真核系统中的高效表达提供了有益的经验。
为提高IL-6在真核系统中的表达效率,我们在构建真核表达载体pcDNA3IL-6的基础上,用表达载体pCI中的CMV启动子和下游所带的β-球蛋白的第一个内含子,置换了pcDNA3中的CMV启动子,构建了一种新的表达载体,使IL-6的表达水平提高了7.5倍。此外,我们还研究了pAdVAntage共转染对IL-6表达的影响,使之表达水平提高了3.6倍。以上结果为细胞因子在真核系统中的高效表达提供了有益的经验。
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- 《中国肿瘤生物治疗杂志》
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.