共查询到17条相似文献,搜索用时 93 毫秒
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目的:研究用冻融的自体胃癌抗原冲击树突状细胞(DC)来诱导肿瘤引流区淋巴结(TDLN)细胞对胃癌细胞系的体外杀伤作用。方法:采用胃癌患者外周血粘附细胞(PBAC),经GM-CSF、IL-4、TNF-α诱导和自体肿瘤冻融抗原(Ag)刺激诱生所获得的DC与TDLN细胞1:50比例共培养3天,获得DC激活的TDLN,即DC-TDLN作效应细胞;分别以Ag和培液代替DC同样培养TDLN,即Ag-TDLN和TDLN作对照,对胃癌细胞系KATO3和黑色素瘤细胞系A375进行杀伤。结果:DC-TDLN、Ag-TDLN、TDLN各组细胞对KATO3,均有显著杀伤活性,其中DC-TDLN组的杀伤作用明显优于后两组,且效靶比20:1的杀伤率优于10:1,显示可能有量效关系;而TDLN各组不同效靶比对A375杀伤率则无显著差异。结论:自PBAC获得的DC,经自身肿瘤Ag冲击并与自身TDLN共培养,可使后者对胃癌细胞系细胞的杀伤作用明显增强。 相似文献
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小鼠肝癌总RNA转染的树突状细胞体外诱导特异性细胞毒T淋巴细胞的研究 总被引:1,自引:0,他引:1
目的 :探讨小鼠骨髓树突状细胞 (dendriticcell,DC)体外经Hepa 1 6肝癌细胞株总RNA转染后 ,对特异性细胞毒T淋巴细胞 (CTL)的诱导作用。方法 :自小鼠骨髓分离DC前体细胞 ,经GM CSF IL 4培养、扩增 ;制备Hepa 1 6小鼠肝癌细胞株总RNA ,体外转染DC ,检测DC诱导同基因型小鼠T细胞增殖及其特异性CTL的反应能力。结果 :经Hepa 1 6肝癌细胞总RNA转染的DC ,其组织相容性分子 (MHC I、II)及共刺激分子 (B7 1 、B7 2 )表达明显增高 ,刺激同基因型小鼠T细胞增殖能力增强 ,且能诱导Hepa 1 6特异性CTL。结论 :以肝癌总RNA转染DC ,构造肝癌疫苗为肝癌的临床治疗提供了新的策略。 相似文献
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毛应华 《国外医学:免疫学分册》2003,26(3):151-154
树突状细胞是已知的功能最强的专职抗原提呈细胞,在抗原的加工提呈、抗原识别及T细胞激活中发挥着重要作用。DC疫苗在部分恶性肿瘤的治疗中取得了令人振奋的效果,是当前抗肿瘤免疫治疗研究的热点之一。 相似文献
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胃癌是我国最常见的消化道恶性肿瘤,治疗效果不理想,预后较差.树突状细胞(DC)是专职的抗原提呈细胞,其在抗肿瘤免疫中发挥了十分重要的作用.大量研究表明,胃癌组织内浸润的DC密度较低的胃癌患者5年生存率较低,预后较差.因此,探索以DC疫苗为基础的胃癌免疫治疗方法将具有十分重要的意义.动物实验证明DC疫苗在小鼠体内显著的抗肿瘤效果.在临床治疗中,DC疫苗在少数胃癌患者治疗中也取得了显著的临床效果.本文综述了DC与肿瘤免疫,与胃癌的诊断、进展、预后,以及与胃癌免疫治疗的研究现状. 相似文献
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人癌胚抗原重组痘苗病毒转染树突状细胞体外诱导的抗肿瘤免疫 总被引:1,自引:0,他引:1
目的:研究人癌胚抗原重组痘苗病毒(rV-CEA)转染外周血树突状细胞(DC)后在外体诱导的抗CEA分泌性肿瘤免疫。方法:分离晚期结肠癌患者的外周血单核细胞,在体外用人重组粒-巨噬细胞集落刺激因子(GM-CSF)及白细胞介素4(IL-4)培养成DC,再用rV-CEA转染DC后激发自体T细胞,观察其体外激发自体T细胞的增殖能力及其诱导的细胞毒性T淋巴细胞(CTL)对自体CEA分泌性肿瘤细胞的杀伤活性,并与野生型痘苗病毒(W-VV)及无病毒转染的DC所激发的T细胞进行比较。结果:经rV-CEA转染的DC能显著刺激自体T细胞的增殖,其激活的T细胞对CEA分泌性自体肿瘤细胞具有特异性杀伤作用。结论:rV-CEA转染的DC可以诱导体CEA分泌性肿瘤免疫。 相似文献
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树突状细胞应用于肿瘤免疫治疗的新进展 总被引:1,自引:0,他引:1
树突状细胞(dendritic cells, DC)是目前所知的机体内功能最强大的抗原提呈细胞, 它通过吞噬、表达、移动等一系列过程, 启动体内免疫系统.而与之相关的肿瘤免疫逃逸或肿瘤转移已成为DC研究的热点.现对DC与肿瘤免疫治疗方面的新进展做一简要综述. 相似文献
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树突状细胞 (DC)是体内功能最强的抗原提呈细胞 (APC) ,也是抗原特异性免疫应答的始动者 ,由DC激活的T细胞介导的免疫应答在机体抗肿瘤过程中起着主导作用。本文主要对DC参与抗肿瘤的机制、DC与肿瘤免疫逃逸的关系及近年来DC在肿瘤生物治疗方面的研究进展作一综述。以DC为基础的肿瘤治疗主要有两种方式 :①免疫治疗 :肿瘤抗原体外冲击致敏DC后回输体内 ;②基因治疗 :以目的基因转染DC后回输体内 相似文献
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转染FasL基因树突状细胞诱导异基因小鼠脾脏T细胞凋亡的研究 总被引:1,自引:0,他引:1
目的 制备稳定表达FasL蛋白的小鼠骨髓源树突状细胞(dendritic cell,DC)并探讨其诱导异基因小鼠脾脏T细胞凋亡的机理.方法 采用培养基选择法体外培养小鼠骨髓源DC,脂质体法转染FasL基因至小鼠成熟DC,实时定量PCR检测转染前后FasL mRNA的表达,流式细胞仪和免疫蛋白印迹检测转染前后FasL蛋白的表达.异系小鼠静脉分别输注未转染DC、转染空质粒DC和转染FasL的DC,7 d后TdT介导的原位末端标记法(TUNEL)和流式细胞仪检测脾脏中T淋巴细胞凋亡.结果 体外培养可获得成熟的小鼠骨髓源DC,转染FasL基因的DC较未转染DC FasL mRNA和FasL蛋白表达明显升高.对脾脏中T淋巴细胞凋亡的检测发现,转染FasL的DC组凋亡指数(11.67±1.53)明显高于未转染DC组(2.67±0.58)和转染空质粒组(3.33±0.58),P<0.01.结论 培养基选择法可收获大量骨髓源DC,脂质体转染FasL基因至小鼠骨髓源DC,可以使DC高表达FasL蛋白.转染FasL的DC输注能明显诱导异系小鼠脾脏T淋巴细胞凋亡. 相似文献
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Dendritic cells as vectors for immunotherapy of tumor and its application for gastric cancer therapy
Dendritic cells(DCs) are recognized as the most potent antigen-presenting cells(APCs) with the ability tostimulate naive resting T cells and initiate primary immune responses.DCs are poised to capture antigen(Ag),migrate to draining lymphoid organs,and,after a process of maturation,select Ag-specific lymphocytes towhich they present the processed Ag,thereby inducing immune responses.Numerous studies indicated thatimmunotherapies utilizing DC-presenting tumor-associated antigens can safely be administered to cancerpatients and induce significant immunologic and clinical responses.Moreover,it has been demonstrated thatDCs are related to clinical stage,invasion,metastasis and prognosis of gastric cancer.DC-based tumor vaccinesbecome a new effective immunoadjuvant therapy for gastric cancer.Cellular & Molecular Immunology.2004;1(5):351-356. 相似文献
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食管癌组织微环境对树突状细胞的影响 总被引:1,自引:0,他引:1
目的:探讨食管癌组织匀浆上清液体外模拟肿瘤微环境对人树突状细胞(DC)分化发育的影响, 揭示肿瘤免疫逃逸机制, 为DC疫苗的应用提供理论基础.方法:制备新鲜食管癌及癌旁组织匀浆上清液, ELISA检测其VEGF-A含量.密度梯度离心法分离人外周血单个核细胞, 含rhGM-CSF和rhIL- 4 RPMI1640培养液诱导DC, 第2天在继续诱导DC基础上设食管癌匀浆上清组、癌旁匀浆上清组、 VEGF-A组, 均隔天半量换液, 第4天加入食管癌细胞株EC9706抗原, 第6天加入脂多糖, 第8天收集各组细胞.观察DC形态, 流式细胞术(FCM)检测免疫表型, RT-PCR检测CD1a表达, CCK-8检测T细胞增殖率及杀伤率.结果:食管癌组织匀浆上清VEGF-A含量[(0.987±0.319) μg/L]明显高于癌旁[(0.152±0.105) μg/L, P<0.05]; 食管癌匀浆上清组细胞形态明显受到抑制, CD86分子阳性率(%)与正常DC相比由69±8降为42±11、 CD1a由56±12降为27±12、 CD11c由21±13降为18±13(P<0.01), CD1a基因几乎无表达, 刺激T细胞增殖率(%)由112.5±7.2降为70.2±3.5(P<0.01), 杀伤率(%)由62.4±0.6 降为46.8±1.6(P<0.01); 癌旁匀浆上清液组、 VEGF-A组结果与正常DC组无统计学意义.结论:食管癌组织匀浆上清液所模拟的微环境对DC的诱导分化及其功能有明显的抑制作用, 在该抑制作用中VEGF-A并不起主要作用. 相似文献
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Immunotherapy can be used to induce immunological tolerance by a number of different protocols. During the last decade the ability to use tolerogenic dendritic cells (DCs) to prevent autoimmunity has received much attention. Many studies have attempted to use immature or semi‐mature DCs to induce tolerance in the non‐obese diabetic (NOD) mouse model of human type 1 diabetes. However, most studies to date have used protocols in which generation of DCs involved a culture step in fetal bovine serum (FBS)‐supplemented medium which may affect tolerance induction in a non‐specific fashion. Indeed, several studies have shown that DCs cultured in the presence of FBS will induce a powerful T helper type 2 (Th2) immune response towards FBS‐related antigens which can suppress an ongoing immune response. Hence, this may interfere with diabetes development in the NOD mouse by induction of immune deviation rather than by antigen‐specific tolerance. In order to test whether antigen‐specific tolerance induction by DC therapy is feasible in the NOD mouse, we therefore generated immature DCs using autologous serum [normal mouse serum (NMS)‐supplemented cultures] instead of FBS, and we show that these DCs can protect NOD mice from diabetes, if pulsed with insulin‐peptide antigens before adoptive transfer. Our data therefore support that DC therapy is able to prevent diabetes in the NOD mouse in an antigen‐specific manner. 相似文献
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Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumour immunity 总被引:4,自引:0,他引:4 下载免费PDF全文
Exosomes (EXO) derived from dendritic cells (DC), which express major histocompatibility complex (MHC) and costimulatory molecules, have been used for antitumour vaccines. However, they are still less effective by showing only prophylatic immunity in animal models or very limited immune responses in clinical trials. In this study, we showed that ovalbumin (OVA) protein-pulsed DC (DC(OVA))-derived EXO (EXO(OVA)) displayed MHC class I-OVA I peptide (pMHC I) complexes, CD11c, CD40, CD80, CCR7, DEC205, Toll-like receptor 4 (TLR4), TLR9, MyD88 and DC-SIGN molecules, but at a lower level than DC(OVA). EXO(OVA) can be taken up by DC through LFA-1/CD54 and C-type lectin/mannose (glucosamine)-rich C-type lectin receptor (CLR) interactions. Mature DC pulsed with EXO(OVA), which were referred to as mDC(EXO), expressed a higher level of pMHC I, MHC II, and costimulatory CD40, CD54 and CD80 than DC(OVA). The mDC(EXO) could more strongly stimulate OVA-specific CD8(+) T-cell proliferation in vitro and in vivo, and more efficiently induce OVA-specific cytotoxic T-lymphocyte responses, antitumour immunity and CD8(+) T-cell memory in vivo than EXO(OVA) and DC(OVA). In addition, mDC(EXO) could also more efficiently eradicate established tumours. Therefore, mature DC pulsed with EXO may represent a new, highly effective DC-based vaccine for the induction of antitumour immunity. 相似文献
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肺癌细胞总RNA转染的DC疫苗体外诱导肺癌患者特异性抗肿瘤免疫的实验研究 总被引:4,自引:0,他引:4
目的:为了探讨肺癌细胞总RNA转染的DC疫苗体外诱导特异性抗肿瘤免疫的能力。方法:采用分离肺癌患者外周血单核细胞体外诱导DC细胞,Trizol法提取肺癌细胞系Calu-6总RNA,用脂质体包裹总RNA转染DC并诱导特异性CTL的扩增,LDH法和ELISA法检测CTL的杀伤活性和IFN-γ分泌。结果:经肺癌细胞总RNA转染的DC特异性表面标志及功能相关分子表达均上调,转染后的DC可显著刺激异体/自体T淋巴细胞增殖,诱导的特异性CTL对携带Calu-6抗原的靶细胞的杀伤率显著高于LAK细胞,再次接触相同抗原时其IFN-γ分泌量显著增高。结论:肺癌细胞总RNA转染的DC疫苗可在体外诱导出特异性抗肿瘤免疫。 相似文献