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极低剂量的T细胞结合抗体使癌症患者肿瘤消退。

Tumor regression in cancer patients by very low doses of a T cell-engaging antibody.

作者信息

Bargou Ralf, Leo Eugen, Zugmaier Gerhard, Klinger Matthias, Goebeler Mariele, Knop Stefan, Noppeney Richard, Viardot Andreas, Hess Georg, Schuler Martin, Einsele Hermann, Brandl Christian, Wolf Andreas, Kirchinger Petra, Klappers Petra, Schmidt Margit, Riethmüller Gert, Reinhardt Carsten, Baeuerle Patrick A, Kufer Peter

机构信息

Interdisciplinary Phase I/II Unit of the University of Würzburg, Klinikstrasse 6-8, 97070 Würzburg, Germany.

出版信息

Science. 2008 Aug 15;321(5891):974-7. doi: 10.1126/science.1158545.

Abstract

Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non-Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell-engaging antibodies appear to have therapeutic potential for the treatment of malignant diseases.

摘要

先前的尝试已显示出T细胞在癌症免疫治疗中的潜力。在此,我们报告一种名为blinatumomab的双特异性抗体构建体的临床活性,它有可能使患者体内所有细胞毒性T细胞参与癌细胞的裂解。在非霍奇金淋巴瘤患者中,每天每平方米低至0.005毫克的剂量导致血液中靶细胞的清除。在0.015毫克的剂量水平首次观察到部分和完全肿瘤消退,在0.06毫克剂量水平接受治疗的所有7名患者均出现肿瘤消退。Blinatumomab还导致骨髓和肝脏中的肿瘤细胞清除。T细胞接合抗体似乎对恶性疾病的治疗具有治疗潜力。

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