Immunotherapy of malignant ascites with trifunctional antibodies
Immunotherapy of malignant ascites with trifunctional antibodies
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DOI：
10.1002/ijc.21165
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发表时间：
2005-11-10
影响因子：
6.4
通讯作者：
Lindhofer, H
中科院分区：
文献类型：
--
作者：
Heiss, MM;Ströhlein, MA;Lindhofer, H
一类新的完整双特异性抗体不仅可以激活 T 细胞，还可以同时激活 I/III+ 型 Fc gamma 受体细胞（巨噬细胞、NK 细胞和 DC），从而显示出未满足的效应子质量。这些三功能抗体 (trAb) 无需任何预刺激或共刺激即可有效特异性杀死目标肿瘤细胞。这一概念在临床情况下对恶性腹水患者进行了体内研究，允许监测肿瘤细胞的消除及其与临床效果的相关性。在一项前瞻性研究中，8 名因腹膜癌病引起的恶性腹水患者接受腹膜内应用 trAb 治疗，该抗体与肿瘤细胞上的 EpCAM 或 Her2/neu 抗原结合。治疗包括在9-23天内施用4-6次，总量为145-940μg。 8 名患者中有 7 名在随访期间或直至死亡时不需要进一步穿刺，平均无穿刺间隔为 38 周（中位数 = 21.5，范围 = 4-136）。肿瘤细胞监测显示，总剂量低至 40-140 μg 时，腹水中的肿瘤细胞已被完全消除。所有患者均出现腹水积聚消失的临床反应，这与肿瘤细胞的消除相关（p = 0.0014）。没有观察到严重的不良事件。临床相关副作用包括发烧、中度腹痛和皮肤反应。 trAb 腹腔内免疫治疗对恶性腹水患者显示出令人信服的疗效。这种治疗为腹膜癌病患者提供了新的治疗选择。 (c) 2005 年 Wiley-Liss, Inc.
A new class of intact bispecific antibodies shows unmet effector qualities by activation of not only T cells but also simultaneous activation of Fc gamma receptor type I/III+ cells (macrophages, NK-cells and DC). These trifunctional antibodies (trAb) lead to efficient specific killing of targeted tumor cells without any pre- or co-stimulation. This concept was investigated in vivo in patients with malignant ascites in a clinical situation that allowed monitoring of tumor cell elimination and correlation with clinical effects. In a prospective study, 8 patients with malignant ascites due to peritoneal carcinomatosis were treated with intraperitoneal application of trAb, which bound either the EpCAM- or Her2/neu-antigen on tumor cells. Treatment consisted of 4-6 applications within 9-23 days with a total amount of 145-940 mu g. Seven of eight patients required no further paracentesis during follow-up or until death with a mean paracentesis-free interval of 38 weeks (median = 21.5, range = 4-136). Tumor cell monitoring showed a complete elimination of tumor cells in ascites already at total doses as low as 40-140 mu g. Clinical response with disappearance of ascites accumulation was seen in all patients, which was correlated with elimination of tumor cells (p = 0.0014). Severe adverse events were not observed. Clinically relevant side effects were fever, moderate abdominal pain and skin reactions. Intraperitoneal immunotherapy with trAb showed convincing efficacy in patients with malignant ascites. This treatment offers new therapeutic options for patients with peritoneal carcinomatosis. (c) 2005 Wiley-Liss, Inc.