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[恶性淋巴瘤的单克隆抗体治疗]

[Monoclonal antibody therapy for malignant lymphoma].

作者信息

Buske Christian, Dreyling Martin, Unterhalt Michael, Hiddemann Wolfgang

机构信息

Medizinische Klinik III, Klinikum der Universität München, Grosshadern, Marchioninistrasse 15, 81377 München.

出版信息

Med Klin (Munich). 2005 Jan 15;100(1):14-24. doi: 10.1007/s00063-005-1115-0.

Abstract

The treatment options for patients with malignant lymphoma have been substantially enriched by the development of B-cell-specific monoclonal antibodies. One of the reasons for the attractiveness of this approach is the different mode of action of these antibodies compared to chemotherapy: they can exert tumor-suppressive effects by at least three major mechanisms: an intrinsic cytotoxic activity, antibody-dependent cellular cytotoxicity (ADCC), and activation of complement-dependent cytolysis (CDC). These monoclonal antibodies can be applied in an unconjugated form or as a carrier of cytotoxic drugs or radioisotopes. The chimeric anti-CD20 antibody rituximab has a direct anti-lymphoma activity, and is highly active in indolent and aggressive lymphoma, in particular in combination with chemotherapy. The anti-CD52 antibody alemtuzumab is effective in the treatment of patients with chronic lymphocytic leukemia (CLL). Another attractive approach is to link anti-CD20 antibodies to radioisotopes, thereby exploiting the radiosensitivity of malignant lymphomas: encouraging results were already presented for the yttrium-90-((90)Y-)labeled anti-CD20 antibody ibritumomab tiuxetan as well as for the iodine-131-((131)I-)labeled anti-CD20 antibody tositumomab.

摘要

B 细胞特异性单克隆抗体的发展极大地丰富了恶性淋巴瘤患者的治疗选择。这种方法具有吸引力的原因之一是,与化疗相比,这些抗体具有不同的作用方式:它们可通过至少三种主要机制发挥肿瘤抑制作用:内在细胞毒性活性、抗体依赖性细胞毒性(ADCC)和补体依赖性细胞溶解(CDC)激活。这些单克隆抗体可以以未偶联的形式应用,也可以作为细胞毒性药物或放射性同位素的载体。嵌合抗 CD20 抗体利妥昔单抗具有直接的抗淋巴瘤活性,在惰性和侵袭性淋巴瘤中具有高度活性,特别是与化疗联合使用时。抗 CD52 抗体阿仑单抗对慢性淋巴细胞白血病(CLL)患者的治疗有效。另一种有吸引力的方法是将抗 CD20 抗体与放射性同位素连接,从而利用恶性淋巴瘤的放射敏感性:钇 - 90(90Y)标记的抗 CD20 抗体替伊莫单抗以及碘 - 131(131I)标记的抗 CD20 抗体托西莫单抗已取得了令人鼓舞的结果。

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