Karagiannis Sophia N, Wang Qin, East Nick, Burke Frances, Riffard Stephane, Bracher Marguerite G, Thompson Richard G, Durham Stephen R, Schwartz Lawrence B, Balkwill Frances R, Gould Hannah J
The Randall Centre, King's College London, London, GB.
Eur J Immunol. 2003 Apr;33(4):1030-40. doi: 10.1002/eji.200323185.
We have previously shown that a chimeric IgE antibody against the folic acid receptor (MOv18 IgE) inhibits tumor growth in a SCID mouse model of ovarian carcinoma. MOv18 IgE gave greater protection than the corresponding chimeric MOv18 IgG1. We have now confirmed these effects in a nude-mouse model of ovarian carcinoma and have demonstrated for the first time that human monocytes are active in IgE antibody-dependent cell-mediated cytotoxicity. Injection of tumor-bearing mice with PBMC and MOv18 IgE led to infiltration of monocytes into the tumors and prolonged survival of the mice. Incubation of PBMC or purified monocytes and MOv18 IgE with ovarian tumor cells in vitro resulted in tumor cell killing proportional to the expression of unoccupied FcepsilonRI on monocytes.We observed phagocytosis of tumor cells by the monocytes in vitro. Our results suggest that tumor-specific IgE antibodies may be exploited for immunotherapy of cancer.
我们之前已经表明,一种针对叶酸受体的嵌合IgE抗体(MOv18 IgE)在卵巢癌的SCID小鼠模型中可抑制肿瘤生长。MOv18 IgE比相应的嵌合MOv18 IgG1提供了更强的保护作用。我们现在已在卵巢癌裸鼠模型中证实了这些效应,并首次证明人类单核细胞在IgE抗体依赖性细胞介导的细胞毒性中具有活性。给荷瘤小鼠注射PBMC和MOv18 IgE导致单核细胞浸润到肿瘤中,并延长了小鼠的存活时间。在体外将PBMC或纯化的单核细胞与MOv18 IgE和卵巢肿瘤细胞一起孵育,导致肿瘤细胞杀伤与单核细胞上未占据的FcepsilonRI的表达成比例。我们在体外观察到单核细胞对肿瘤细胞的吞噬作用。我们的结果表明,肿瘤特异性IgE抗体可用于癌症的免疫治疗。