人卵巢癌细胞与自体或同种异体树突状细胞融合诱导抗肿瘤免疫(英文)

Induction of anti-tumor activity by immunization with fusion of human ovarian carcinoma cells to autologous or allogeneic dendritic cells

目的 探讨人卵巢癌 (OVCA)细胞与自体或同种异体树突状细胞 (DC)融合后体外诱导特异性CTL的作用。方法 用PEG法将OVCA细胞与自体或异体DC融合 ,在含GM -CSF的RPNH - 16 4 0完全培养基中继续培养 7～ 14d ,然后将融合细胞与CA - 12 5特异性T细胞共同培养 ,用细胞内细胞素染色法检测其诱导CTL活性。结果 人类OVCA细胞表达CA - 12 5、HER2A/neu、MUC1肿瘤相关抗原及MHC -Ⅰ类分子和粘附分子 (ICAM ) ,但不表达MHC -Ⅱ类分子、B7- 1和B7- 2 ;DC则表达MHC -Ⅰ类和Ⅱ类分子、共刺激分子和ICAM ,但不表达DF3/MUC1或CA - 12 5等OVCA相关抗原 ,而OVCA细胞与自体或异体DC融合细胞则表达CA - 12 5及MUC1肿瘤相关抗原、MHC -Ⅰ类和Ⅱ类分子、B7- 1、B7- 2及ICAM。结论 人OVCA与自体或异体DC融合细胞能诱导由MHC -Ⅰ类分子限制的CTL活性和自体肿瘤细胞的溶解作用。

Objective:To study the effect of activation of specific anti-tumor cytotoxic T lymphocytes in vitro by fusion of human ovarian carcinoma cells with autologous or allogeneic dendritic cells.Methods:The human dendritic cells with ovarian carcinoma cells were fused by PEG and were cultivated in complete RPMI-1640 media containing 10% FCS, GM-CSF for 7～14 days,and then co-cultured fusion cells with CA-125 Specific T cells. The activation of anti-tumor CTL elicited by the fusion cells was detected by intracellular cytokine staining.Results:The human ovarian carcinoma cells expressed the CA-125,MUC1,MHC classⅠand ICAM, but not MHCclassⅡ,B7-1 or B7-2.In contrast, the DCs expressed MHC classⅠand class Ⅱ molecules, co-stimulative molecules and ICAM, but not CA-125 or MUC1 carcinoma-associated Ags. Fusion of the OVCA cells to autologous or allogeneic DCs resulted in the generation of heterokaryons that expressed the CA-125 and MUC1 Ags, MHC class Ⅰand classⅡ molecules,B7-1 and B7-2.Conclusions:The fusions of autologous or allogeneic DCs with ovarian carcinoma cells can induce cytotoxic T cell activity and lysis of autologous tumor cells by a MHCclassⅠ-restricted mechanism.