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Volume 4,Issue 4,1997 Table of Contents
1997, 4(4):259-263.
DOI: 10.3872/j.issn.1007-385X.1997.4.003
Abstract:
A main complication of chemotherapy in cancer patients is hematopoiesis suppression. Microenviroment transplantation using bone marrow stromal cells (BMSCs) has been demonstrated to be a potent method in recovery of hematopoiesis in animal models. Based on hematopoiesis-supportive ability of BMSCs and high potency of IL-3 in hematopoiesis stimulation, BMSCs were studied as a cellular delivery system for IL-3 gene transfection to promote hematopoiesis recovery of mice after high dose chemotherapy. BMSCs were transfected with recombinant adenovirous containing murine IL-3 gene(MOI = 10), the level of mIL-3 secreted by gene-modified BMSCs was 110U/ml/10~6 cells/ 24h in vitro. The mice were injected with high dose cyclophosphamide(200mg/kg) i.p. and after 24 hours the IL-3 gene-modified BMSCs(2 x 10~6/mouse) were transplanted intrasplenically. White blood cell counts in peripheral blood of mice received intrasplenic injection of IL-3-BMSCs were kept at a high level within two weeks after chemotherapy. The pathological sections of spleens and bone marrow showed significant recovery of hematopoiesis, compared with that of mice received chemotherapy only. The data indicated the feasibility of IL-3 gene-modified BMSCs transplantation in the acceleration of hematopoiesis recovery after chemotherapy.
A main complication of chemotherapy in cancer patients is hematopoiesis suppression. Microenviroment transplantation using bone marrow stromal cells (BMSCs) has been demonstrated to be a potent method in recovery of hematopoiesis in animal models. Based on hematopoiesis-supportive ability of BMSCs and high potency of IL-3 in hematopoiesis stimulation, BMSCs were studied as a cellular delivery system for IL-3 gene transfection to promote hematopoiesis recovery of mice after high dose chemotherapy. BMSCs were transfected with recombinant adenovirous containing murine IL-3 gene(MOI = 10), the level of mIL-3 secreted by gene-modified BMSCs was 110U/ml/10~6 cells/ 24h in vitro. The mice were injected with high dose cyclophosphamide(200mg/kg) i.p. and after 24 hours the IL-3 gene-modified BMSCs(2 x 10~6/mouse) were transplanted intrasplenically. White blood cell counts in peripheral blood of mice received intrasplenic injection of IL-3-BMSCs were kept at a high level within two weeks after chemotherapy. The pathological sections of spleens and bone marrow showed significant recovery of hematopoiesis, compared with that of mice received chemotherapy only. The data indicated the feasibility of IL-3 gene-modified BMSCs transplantation in the acceleration of hematopoiesis recovery after chemotherapy.
1997, 4(4):264-267.
DOI: 10.3872/j.issn.1007-385X.1997.4.004
Abstract:
CTL responses by autologous colorectal cancer cells were observed in five cases. The specific CTL was induced from two cases, in which tumor associated antigen, CA-Hb_3, was strongly positive. The CTL could not induced from other three cases in which CA-Hb_3 antigen was weakly positive. Weakly positive tumor cells in the three cases were loaded CA-Hb_3 antigen into cytoplasmas by the cationic liposomes and tested by immunohistochemical assay. The results showed that CA-Hb_3 antigen of tumor cells in two cases changed to strongly positive, and could induce CTL responses successfully. With blocking agents BFA and anti-MHC-I monoclonal antibody, CTL responses could be blocked. Our results suggested that soluble CA-Hb_3 antigen could enhance the immunogenity of colorectal cancer cells and induce effective anti-tumor cellular immune responses.
CTL responses by autologous colorectal cancer cells were observed in five cases. The specific CTL was induced from two cases, in which tumor associated antigen, CA-Hb_3, was strongly positive. The CTL could not induced from other three cases in which CA-Hb_3 antigen was weakly positive. Weakly positive tumor cells in the three cases were loaded CA-Hb_3 antigen into cytoplasmas by the cationic liposomes and tested by immunohistochemical assay. The results showed that CA-Hb_3 antigen of tumor cells in two cases changed to strongly positive, and could induce CTL responses successfully. With blocking agents BFA and anti-MHC-I monoclonal antibody, CTL responses could be blocked. Our results suggested that soluble CA-Hb_3 antigen could enhance the immunogenity of colorectal cancer cells and induce effective anti-tumor cellular immune responses.
1997, 4(4):268-272.
DOI: 10.3872/j.issn.1007-385X.1997.4.005
Abstract:
针对慢性粒细胞白血病(CML)特征基因bcr/abl的嵌合位点和CML相关癌基因c-myb的第2外显子分别设计、合成的反义寡聚脱氧核苷酸asODN及其硫代磷酸化修饰物s-asODN分别或联合作用于慢性粒细胞白血病细胞株K562.结果表明各种asODN可显著抑制K562细胞的存活,最大抑制率为64.7%±3.2%,可显著抑制K562细胞的DNA合成,最大抑制率为85.8%±4.1%,可显著降低甚至几乎完全抑制bcr/abl的转录,可显著诱导K562发生凋亡.s-asODN的作用效果显著优于未加修饰的对应asODN.联合使用bcr/abl与c-myb的ASO比单独使用其中之一效果更佳.各种作用效果均表现出片断、时间相关性.这些说明,bcr/abl在CML发病机制中起双重作用,不仅刺激了CML细胞的过度增殖,而且抑制了细胞的凋亡.c-myb可能主要通过对bcr/abl的调控而与CML相关.asODN修饰物及多个癌基因的asODN联合使用可能是反义基因治疗的发展方向.
针对慢性粒细胞白血病(CML)特征基因bcr/abl的嵌合位点和CML相关癌基因c-myb的第2外显子分别设计、合成的反义寡聚脱氧核苷酸asODN及其硫代磷酸化修饰物s-asODN分别或联合作用于慢性粒细胞白血病细胞株K562.结果表明各种asODN可显著抑制K562细胞的存活,最大抑制率为64.7%±3.2%,可显著抑制K562细胞的DNA合成,最大抑制率为85.8%±4.1%,可显著降低甚至几乎完全抑制bcr/abl的转录,可显著诱导K562发生凋亡.s-asODN的作用效果显著优于未加修饰的对应asODN.联合使用bcr/abl与c-myb的ASO比单独使用其中之一效果更佳.各种作用效果均表现出片断、时间相关性.这些说明,bcr/abl在CML发病机制中起双重作用,不仅刺激了CML细胞的过度增殖,而且抑制了细胞的凋亡.c-myb可能主要通过对bcr/abl的调控而与CML相关.asODN修饰物及多个癌基因的asODN联合使用可能是反义基因治疗的发展方向.
1997, 4(4):273-277.
DOI: 10.3872/j.issn.1007-385X.1997.4.006
Abstract:
用湖南鼻咽癌细胞株HNI2为免疫原,制备了数株抗鼻咽癌单抗（Abl）.再用两株Abl（FC2、HNI-5）为免疫原,制备了两株抗独特型单抗Ab2（2H4和5D3）.体外和体内实验证实,2H4、5D3能替代鼻咽癌抗原,诱导体液和细胞免疫应答.因而认为它们可以作为新型抗鼻咽癌疫苗的候选物.选择19例晚期鼻咽癌病人用氢氧化铝凝胶沉淀的Ab2（Alum-2H4、Alum5D3）,配合放疗进行主动免疫治疗;9例单纯接受放疗的晚期鼻咽癌病人作为对照组.经血清学检测发现,治疗组病人的抗抗独特型抗体（Ab3）、抗肿瘤抗体（Ab1’）水平均有不同程度增高,但也产生了人抗鼠抗体（HAMA）.血清细胞因子TNF-α、IFN-γ、IL-2水平在大多数治疗组病人中升高,而对照组Ab1 TNF-α、IFN-γIFM及IL-2血清水平均未升高.初步临床研究显示,鼠源性抗独特型单抗用于临床治疗是安全的,且Ab2能模拟肿瘤相关抗原,激发机体产生主动免疫应答.
用湖南鼻咽癌细胞株HNI2为免疫原,制备了数株抗鼻咽癌单抗（Abl）.再用两株Abl（FC2、HNI-5）为免疫原,制备了两株抗独特型单抗Ab2（2H4和5D3）.体外和体内实验证实,2H4、5D3能替代鼻咽癌抗原,诱导体液和细胞免疫应答.因而认为它们可以作为新型抗鼻咽癌疫苗的候选物.选择19例晚期鼻咽癌病人用氢氧化铝凝胶沉淀的Ab2（Alum-2H4、Alum5D3）,配合放疗进行主动免疫治疗;9例单纯接受放疗的晚期鼻咽癌病人作为对照组.经血清学检测发现,治疗组病人的抗抗独特型抗体（Ab3）、抗肿瘤抗体（Ab1’）水平均有不同程度增高,但也产生了人抗鼠抗体（HAMA）.血清细胞因子TNF-α、IFN-γ、IL-2水平在大多数治疗组病人中升高,而对照组Ab1 TNF-α、IFN-γIFM及IL-2血清水平均未升高.初步临床研究显示,鼠源性抗独特型单抗用于临床治疗是安全的,且Ab2能模拟肿瘤相关抗原,激发机体产生主动免疫应答.
1997, 4(4):281-283.
DOI: 10.3872/j.issn.1007-385X.1997.4.008
Abstract:
本文研究了硒酸酯多糖(KSC)对荷S180肉瘤小鼠NK细胞活性、LAK细胞活性、IL-2分泌能力和自身肿瘤杀伤活性(ATK)的影响及抑癌效应.结果表明,KSC(40mg/kg·d×9d,ig)能增强荷瘤鼠NK细胞和LAK细胞活性,促进脾细胞产生IL-2,增强ATK活性;加强环磷酰胺(Cy,20mg/kg·d×9d,ip)的抑瘤作用,并能拮抗Cy对免疫活性细胞的抑制效应.体外用rIL-2激活荷瘤鼠脾淋巴细胞可诱生或增强ATK活性.本研究结果提示,KSC上调肿瘤宿主NK细胞和LAK细胞活性及IL-2的分泌水平,增强ATK活性,可作为生物反应调节剂(BRM)应用于肿瘤生物治疗.
本文研究了硒酸酯多糖(KSC)对荷S180肉瘤小鼠NK细胞活性、LAK细胞活性、IL-2分泌能力和自身肿瘤杀伤活性(ATK)的影响及抑癌效应.结果表明,KSC(40mg/kg·d×9d,ig)能增强荷瘤鼠NK细胞和LAK细胞活性,促进脾细胞产生IL-2,增强ATK活性;加强环磷酰胺(Cy,20mg/kg·d×9d,ip)的抑瘤作用,并能拮抗Cy对免疫活性细胞的抑制效应.体外用rIL-2激活荷瘤鼠脾淋巴细胞可诱生或增强ATK活性.本研究结果提示,KSC上调肿瘤宿主NK细胞和LAK细胞活性及IL-2的分泌水平,增强ATK活性,可作为生物反应调节剂(BRM)应用于肿瘤生物治疗.
1997, 4(4):287-291.
DOI: 10.3872/j.issn.1007-385X.1997.4.010
Abstract:
本研究应用125I-UdR释放实验,测定了大量随机取样于111位癌症患者的外周血淋巴细胞以及从它们中诱导出的处于不同培养期的淋巴因子激活的杀伤细胞对K562和Raji肿瘤细胞的体外细胞毒活性.对560个有效数据的统计分析,获得以下结果:1.经过培养系统的作用,对K562细胞的细胞毒活性,从培养前的34.78±25%上升到8～13天培养期的68.04±17.3%之后基本稳定于近70%的水平,直至23～27天的培养期.此细胞毒活性的构成比模式表明,在培养之前,样品分布于很广的活性区域（10～90%）;培养 8～13天和以后的培养期,约85%的样品集中到高活性区域（50～95%）.2.对 Raji细胞的细胞毒活性,从培养前的8.9±8%上升到8～13天培养期的42.1±22%之后,在随后的培养期中,维持于约35%的水平.对Raji的细胞毒活性的构成比显示,在培养前,全部样品处于低活性区域（<25%）;在培养过程中,部分样品（约30%）向高活性区域发生明显的扩展（50～90%）,但另一部份样品（约40%）一直位于低活性区域（<35%）.这样形成高低两个分布区域.这种现象的机理值得进一步探讨.
本研究应用125I-UdR释放实验,测定了大量随机取样于111位癌症患者的外周血淋巴细胞以及从它们中诱导出的处于不同培养期的淋巴因子激活的杀伤细胞对K562和Raji肿瘤细胞的体外细胞毒活性.对560个有效数据的统计分析,获得以下结果:1.经过培养系统的作用,对K562细胞的细胞毒活性,从培养前的34.78±25%上升到8～13天培养期的68.04±17.3%之后基本稳定于近70%的水平,直至23～27天的培养期.此细胞毒活性的构成比模式表明,在培养之前,样品分布于很广的活性区域（10～90%）;培养 8～13天和以后的培养期,约85%的样品集中到高活性区域（50～95%）.2.对 Raji细胞的细胞毒活性,从培养前的8.9±8%上升到8～13天培养期的42.1±22%之后,在随后的培养期中,维持于约35%的水平.对Raji的细胞毒活性的构成比显示,在培养前,全部样品处于低活性区域（<25%）;在培养过程中,部分样品（约30%）向高活性区域发生明显的扩展（50～90%）,但另一部份样品（约40%）一直位于低活性区域（<35%）.这样形成高低两个分布区域.这种现象的机理值得进一步探讨.
1997, 4(4):294-297.
DOI: 10.3872/j.issn.1007-385X.1997.4.012
Abstract:
应用抗CD3单抗和人rIL-2共同诱导人外周血单个核细胞制备人CD3AK细胞(CDAK).采用LDH释放法、ABC-CELISA法、流式细胞术等方法观察了CD3AK杀伤癌细胞的机理及人rIFN-α、rIFN-γ、rTNF细胞因子、化疗药顺氨氯铂(CDDP)和阿霉素(ADM)对CD3AK杀伤活性的调控效应.结果表明,①粘附分子ICAM-1/LFA-1参与CD3AK的杀瘤过程,并且rIFN-α、rTNF的促CD3AK杀伤效应亦是通过上述途径实现的.③CD3AK通过分泌可溶性杀伤因子间接杀伤癌细胞.③CD3AK通过膜相关TNF参与杀伤效应.④CD3AK介导癌细胞凋亡.⑤化疗药CDDP和ADM处理癌细胞后,提高其对CD3AK杀伤活性的敏感性,CDDP促杀伤效应与其上调癌细胞表面ICAM-1、HLA-ABC抗原表达有关.
应用抗CD3单抗和人rIL-2共同诱导人外周血单个核细胞制备人CD3AK细胞(CDAK).采用LDH释放法、ABC-CELISA法、流式细胞术等方法观察了CD3AK杀伤癌细胞的机理及人rIFN-α、rIFN-γ、rTNF细胞因子、化疗药顺氨氯铂(CDDP)和阿霉素(ADM)对CD3AK杀伤活性的调控效应.结果表明,①粘附分子ICAM-1/LFA-1参与CD3AK的杀瘤过程,并且rIFN-α、rTNF的促CD3AK杀伤效应亦是通过上述途径实现的.③CD3AK通过分泌可溶性杀伤因子间接杀伤癌细胞.③CD3AK通过膜相关TNF参与杀伤效应.④CD3AK介导癌细胞凋亡.⑤化疗药CDDP和ADM处理癌细胞后,提高其对CD3AK杀伤活性的敏感性,CDDP促杀伤效应与其上调癌细胞表面ICAM-1、HLA-ABC抗原表达有关.
1997, 4(4):298-301.
DOI: 10.3872/j.issn.1007-385X.1997.4.013
Abstract:
An eukaryotic expression plasmid Rc/CMV GHcDNA containing CMV late promoter and hGH cDNA was constructed and introduced into mouse skeletal muscle by means of direct injection with or without the cationic liposome (Lipofectin and Lipofectamine reagent) intramuscularly. The expression of the gene was detected through both RT-PCR and IRMA (Immunoradiometric assay) at the level of transcription and protein respectively. The gene expression can be detected even after 90 days of single plasmid injection. Compared with the mice injected with the plasmid itself, the expression levels of mice injected with the plasmid-cationic liposome complex seem to be higher, and the expression period longer. Furthermore, the effect of Lipofectamine seems to be even better than that of Lipofectin. The results indicate that direct intramuscular injection with recombinant expression plasmid or plasmid-cationic liposome complex is a simple, efficient and economical way for foreign gene transfer and expression in experimental mice in vivo.
An eukaryotic expression plasmid Rc/CMV GHcDNA containing CMV late promoter and hGH cDNA was constructed and introduced into mouse skeletal muscle by means of direct injection with or without the cationic liposome (Lipofectin and Lipofectamine reagent) intramuscularly. The expression of the gene was detected through both RT-PCR and IRMA (Immunoradiometric assay) at the level of transcription and protein respectively. The gene expression can be detected even after 90 days of single plasmid injection. Compared with the mice injected with the plasmid itself, the expression levels of mice injected with the plasmid-cationic liposome complex seem to be higher, and the expression period longer. Furthermore, the effect of Lipofectamine seems to be even better than that of Lipofectin. The results indicate that direct intramuscular injection with recombinant expression plasmid or plasmid-cationic liposome complex is a simple, efficient and economical way for foreign gene transfer and expression in experimental mice in vivo.
1997, 4(4):302-306.
DOI: 10.3872/j.issn.1007-385X.1997.4.014
Abstract:
树突状细胞(DC)作为抗原提呈细胞,在激发T细胞免疫应答及T细胞依赖性抗体生成中起重要作用,骨髓及外周血的CD34造血前体细胞在GM-CSF和TNF-α的作用下,可在体外分化发育,生成树突状细胞.本研究从正常人外周血分离获得单核细胞,加入100ng/ml hGM-CSF、500U/ml hIL-4,体外培养1周后,获得大量高纯度的树突状细胞,其高表达MHC-Ⅰ、MHC-Ⅱ类分子及共刺激分子B7-1和CD40,能强烈激发同种异体T淋巴细胞增殖,培养条件以应用自体血清或胎牛血清为最佳;单独应用hGM-CSF只能生成巨噬细胞;在培养末期加入TNFα可促进DC进一步成熟.本研究为DC的深入研究与临床应用奠定了基础.
树突状细胞(DC)作为抗原提呈细胞,在激发T细胞免疫应答及T细胞依赖性抗体生成中起重要作用,骨髓及外周血的CD34造血前体细胞在GM-CSF和TNF-α的作用下,可在体外分化发育,生成树突状细胞.本研究从正常人外周血分离获得单核细胞,加入100ng/ml hGM-CSF、500U/ml hIL-4,体外培养1周后,获得大量高纯度的树突状细胞,其高表达MHC-Ⅰ、MHC-Ⅱ类分子及共刺激分子B7-1和CD40,能强烈激发同种异体T淋巴细胞增殖,培养条件以应用自体血清或胎牛血清为最佳;单独应用hGM-CSF只能生成巨噬细胞;在培养末期加入TNFα可促进DC进一步成熟.本研究为DC的深入研究与临床应用奠定了基础.
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- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
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- 刊号：ISSN 1007-385X
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.