负载辐射凋亡MB49肿瘤细胞抗原的树突状细胞(DC)疫苗对小鼠膀胱癌的抑制作用
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摘要
目的研究辐射凋亡MB49肿瘤细胞诱导的树突状细胞(dendritic cell,DC)疫苗的制备及对C57BL/6小鼠体内膀胱肿瘤的免疫学效应。方法采用辐射法获取MB49细胞抗原并用其致敏骨髓来源的DC来制备DC疫苗。用MB49小鼠膀胱癌细胞建立荷瘤动物模型,随机分为实验组和对照组,于肿瘤细胞接种后第7、14天给予相应DC疫苗治疗或者PBS,每组分为2个亚组,分别用于测量瘤质量、体积及用于观察荷瘤小鼠存活情况。结果负载辐射凋亡肿瘤细胞DC疫苗的实验组荷瘤小鼠,其肿瘤的平均体积和平均质量均显著低于对照组(P<0.01),生存期长于对照组。DC疫苗实验组中有2只小鼠30天内无肿瘤生长,再次皮下接种MB49细胞观察30天仍无肿瘤发生。结论负载辐射凋亡肿瘤细胞的DC疫苗对膀胱肿瘤荷瘤小鼠具有抑瘤效应和延长生存期的作用。
Objective To investigate the effects of dendritic cell(DC)vaccine sensitized by antigen with irradiated apoptotic MB49tumor cells on the treatment of bladder cancer in mice. Methods MB49antigen was obtained by irradiation and then sensitized bone marrow derived DC(BM-DC)to establish DC vaccine. Mice bearing bladder cancer were divided into DC group and control group.On the 7th and 14th day after subcutaneous of tumor cell,DC group was injected DC vaccine,and the control group was injected PBS.Each group was divided into two subgroups in order to measure tumor mass and volume and to observe survival condition of mice. Results The average mass and volume of tumors in mice of DC group were significantly higher than those of the control group(P<0.01),which also had longer survival period.Two mice in DC group survived without tumor for 30days.Although they were injected MB49cells for the second time,there was no tumor growth in 30days. Conclusions DC vaccine loading antigen with irradiated apoptotic MB49 tumor cells can inhibit the growth of MB49cells in vivo.
Objective To investigate the effects of dendritic cell(DC)vaccine sensitized by antigen with irradiated apoptotic MB49tumor cells on the treatment of bladder cancer in mice. Methods MB49antigen was obtained by irradiation and then sensitized bone marrow derived DC(BM-DC)to establish DC vaccine. Mice bearing bladder cancer were divided into DC group and control group.On the 7th and 14th day after subcutaneous of tumor cell,DC group was injected DC vaccine,and the control group was injected PBS.Each group was divided into two subgroups in order to measure tumor mass and volume and to observe survival condition of mice. Results The average mass and volume of tumors in mice of DC group were significantly higher than those of the control group(P<0.01),which also had longer survival period.Two mice in DC group survived without tumor for 30days.Although they were injected MB49cells for the second time,there was no tumor growth in 30days. Conclusions DC vaccine loading antigen with irradiated apoptotic MB49 tumor cells can inhibit the growth of MB49cells in vivo.
引文
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[3]Koido S,Homma S,Hara E,et al.Regulation of tumor immunity by tumor/dendritic cell fusions[J].Clin Dev Immunol,2010:516768.
[4]von Euw EM,Barrio MM,Furman D,et al.A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells.Analysis of toxicity and immune response to the vaccine and of IL-10-1082promoter genotype as predictor of disease progression[J].J Transl Med,2008,6:6.
[5]Steinman RM,Pope M.Exploiting dendritic cells to improve vaccine efficacy[J].Clin Invest,2002,109(12):1519-1526.
[6]Yanofsky VR,Mitsui H,Felsen D,et al.Understanding dendritic cells and their role in cutaneous carcinoma and cancer immunotherapy[J].Clin Dev Immunol,2013:624123.
[7]Li YL,Wu YG,Wang YQ,et al.Bone marrow-derived dendritic cells pulsed with tumor lysates induce anti-tumor immunity against gastric cancer ex vivo[J].World J Gastroenterol,2008,14(46):7127-7132.
[8]Fry TJ,Shand JL,Milliron M,et al.Antigen loading of DCs with irradiated apoptotic tumor cells induces improved anti-tumor immunity compared to other approaches[J].Cancer Immunol Immunother,2009,58(8):1257-1264.
[9]Hoffmann TK,Meidenbauer N,Dworacki G,et al.Generation of tumor-specific T-lymphocytes by crosspriming with human dendritic cells ingesting apoptotic tumor cells[J].Cancer Res,2000,60(13):3542-3549.
[10]Albert ML,Jegathesan M,Darnell RB.Dendritic cell maturation is required for the cross-tolerization of CD8+T cells[J].Nat Immunol,2001,2(11):1010-1017.