Trastuzumab activates allogeneic or autologous antibody-dependent cellular cytotoxicity against malignant rhabdoid tumor cells and interleukin-2 augments the cytotoxicity
Trastuzumab activates allogeneic or autologous antibody-dependent cellular cytotoxicity against malignant rhabdoid tumor cells and interleukin-2 augments the cytotoxicity
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DOI：
10.1158/1078-0432.ccr-07-1661
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发表时间：
2008-02-15
影响因子：
11.5
通讯作者：
Sugimoto, Tohru
中科院分区：
文献类型：
--
作者：
Katsumi, Yoshiki;Kuwahara, Yasumichi;Sugimoto, Tohru
目的：恶性横纹肌样瘤（Malignant rhabdoid tumor，MRT）是一种预后不良的儿童早期恶性肿瘤.曲妥珠单抗是一种抗人表皮生长因子受体-2（HER-2）的人源化单克隆抗体，已被证明对乳腺癌和其他癌症有效。我们研究了曲妥珠单抗对MRT细胞株的影响。实验设计：我们通过间接免疫荧光，流式细胞术和免疫组化检测HER-2在四种MRT细胞株和两种肿瘤组织中的表达。通过细胞生长试验检查曲妥珠单抗对MRT细胞的作用。为了观察效应细胞的抗体依赖性细胞毒性，我们研究了曲妥珠单抗与异基因或自体人外周血单个核细胞的细胞毒性与IL-2使用铬释放assay.Results：所有四个MRT细胞系和两个MRT组织表达HER-2蛋白。单独的曲妥珠单抗不降低MRT细胞系的活力。另一方面，异基因和自体外周血单个核细胞的存在显著增加曲妥珠单抗对每种MRT细胞系的细胞毒性（P < 0.01）。HER-2表达与曲妥珠单抗增强细胞毒作用之间存在强相关性（r = 0.825）。此外，曲妥珠单抗联合白细胞介素-2（IL-2）增强的外周血单核细胞的细胞毒性显著高于曲妥珠单抗单独或IL-2单独（P < 0.01）。结论：我们的研究结果表明：（1）曲妥珠单抗可以通过效应细胞的抗体依赖性细胞毒性作用对MRT细胞发挥抗肿瘤作用;（2）IL-2可以增强曲妥珠单抗对MRT细胞的细胞毒性。
Purpose: Malignant rhabdoid tumor (MRT) is an early childhood cancer with poor prognosis. Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor-2 (HER-2), has been shown to be effective against breast cancer and other cancers. We investigated the effect of trastuzumab on MRT cell lines.Experimental Design: We examined expression of HER-2 on four MRT cell lines and two tumor tissues by indirect immunofluorescence, flow cytometry, and immunohistochemistry. The effect of trastuzumab against MRT cells was examined by cell growth assay. To observe the antibody-dependent cellular cytotoxicity of effector cells, we examined the cytotoxicity of trastuzumab in combination with allogeneic or autologous human peripheral blood mononuclear cells with and without IL-2 using the chromium release assay.Results: All four MRT cell lines and both MRT tissues expressed HER-2 protein. Trastuzumab alone did not reduce the viability of the MRT cell lines. On the other hand, the cytotoxicity of trastuzumab against each of the MRT cell lines was significantly increased by the presence of allogeneic and autologous peripheral blood mononuclear cells (P < 0.01). There was a strong correlation coefficient (r = 0.825) between HER-2 expression and the cytotoxicity enhanced by trastuzumab. Moreover, trastuzumab in combination with peripheral blood mononuclear cells augmented by interleukin-2 (IL-2) was significantly more cytotoxic than trastuzumab alone or IL-2 alone (P < 0.01).Conclusions: Our results indicate that (1) trastuzumab can exert antitumor effects on MRT cells by using the anti body-dependent cellular cytotoxicity of effector cells and (2) IL-2 can enhance the cytotoxicity of trastuzumab against MRT cells.