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据8月14日的《科学》杂志报道说,T 细胞是一种在与癌症肿瘤的斗争中有前途的特别的免疫细胞;但肿瘤细胞与正常的人类细胞很好地混合在一起,因此要找到一种使得这些T 细胞能够标靶肿瘤细胞的技术一直难以成功。但是现在研究人员说,他们已经研发出了一种抗体蛋白,它能够有效地将非何杰金氏淋巴瘤病人的T 细胞与肿瘤细胞结合起来,导致该癌症的可测出的或是完全的消退。
这种被称作blinatumomab 的抗体看来对恶性肿瘤会有重大的治疗潜力。Ralf Bargou 及其同僚在病人中尝试了不同剂量的blinatumomab,结果发现,在38 名病人中,在每天每平方米0.0005-0.006 毫克的剂量范围内,有11 名病人出现了明显的治疗反应和肿瘤的消退。然而,也有相关的不良反应出现。现在有一个正在进行的临床II 期试验在研究blinatumomab 在淋巴细胞性白血病患者中的活性。
Science 15 August 2008 321: 974-977 [DOI: 10.1126/science.1158545]
Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
Ralf Bargou,1,2* Eugen Leo,3*{dagger} Gerhard Zugmaier,3 Matthias Klinger,3 Mariele Goebeler,1,2 Stefan Knop,2 Richard Noppeney,4 Andreas Viardot,5 Georg Hess,6 Martin Schuler,7 Hermann Einsele,2 Christian Brandl,3 Andreas Wolf,3 Petra Kirchinger,3 Petra Klappers,3 Margit Schmidt,3 Gert Riethmüller,8 Carsten Reinhardt,3 Patrick A. Baeuerle,3{ddagger} Peter Kufer3
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.
1 Interdisciplinary Phase I/II Unit of the University of Würzburg, Klinikstraße 6-8, 97070 Würzburg, Germany.
2 Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Klinikstraße 6-8, 97070 Würzburg, Germany.
3 Micromet AG, Staffelseestraße 2, 81477 Munich, Germany; and Micromet, Incorporated, 6707 Democracy Boulevard, Bethesda, MD 20817, USA.
4 Universitätsklinikum Essen, Klinik für Hämatologie, Medizinische Klinik und Poliklinik, Hufelandstraße 55, 45147 Essen, Germany.
5 Universitätsklinikum Ulm, Innere Medizin III, Robert-Koch-Straße 8, 89081 Ulm, Germany.
6 Klinikum der Johannes-Gutenberg Universität III, Medizinische Klinik und Poliklinik, Langenbeckstraße 1, 55131 Mainz, Germany.
7 Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Tumorforschung, Hufelandstraße 55, 45122 Essen, Germany.
8 Institute for Immunology, Ludwig-Maximilians-Universität, Goethestraße 31, 81333 Munich, Germany. |
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