Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
Am J Obstet Gynecol. 2011 Dec;205(6):567.e1-7. doi: 10.1016/j.ajog.2011.06.093. Epub 2011 Jul 13.
We evaluated the expression of human trophoblast cell-surface marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, against treatment-refractory cervical cancer.
Trop-2 expression was evaluated by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. Sensitivity to hRS7 antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in 5-hour chromium release assays. The effect of interleukin (IL)-2 on hRS7 ADCC was also investigated.
Membrane Trop-2 expression was observed in 8 of 8 (100%) of the cancer samples tested by immunohistochemistry, but not in normal cervix. High messenger RNA expression by real-time polymerase chain reaction and high Trop-2 surface expression by flow cytometry were detected in 80% of cervical cancers (4 of 5 cell lines). Although these tumors were resistant to natural killer cell-dependent cytotoxicity in vitro (mean killing, 6.0%), Trop-2-positive cell lines showed high sensitivity to hRS7 ADCC (range of killing, 30.6-73.2%). Incubation with IL-2 further increased the level of cytotoxicity against Trop-2-positive tumors.
hRS7 may represent a novel treatment option for patients with cervical cancer refractory to conventional treatment modalities.
我们评估了人滋养细胞表面标志物（Trop-2）的表达以及 hRS7（一种人源化单克隆抗 Trop-2 抗体）对治疗抵抗性宫颈癌的潜力。
通过免疫组织化学、实时聚合酶链反应和流式细胞术评估 Trop-2 表达。通过 5 小时铬释放试验测试 hRS7 抗体依赖性细胞介导的细胞毒性（ADCC）和补体依赖性细胞毒性的敏感性。还研究了白细胞介素（IL）-2 对 hRS7 ADCC 的影响。
免疫组织化学检测到 8 个（100%）癌症样本中存在膜 Trop-2 表达，但在正常宫颈中不存在。实时聚合酶链反应的高信使 RNA 表达和流式细胞术的高 Trop-2 表面表达在 80%的宫颈癌（5 个细胞系中的 4 个）中检测到。尽管这些肿瘤在体外对自然杀伤细胞依赖性细胞毒性具有抗性（平均杀伤率为 6.0%），但 Trop-2 阳性细胞系对 hRS7 ADCC 表现出高敏感性（杀伤范围为 30.6%-73.2%）。与 IL-2 孵育进一步增加了针对 Trop-2 阳性肿瘤的细胞毒性水平。
hRS7 可能代表一种治疗对常规治疗方式有抵抗性的宫颈癌患者的新选择。
