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未偶联的CD30单克隆抗体对人间变性大细胞淋巴瘤异种移植瘤的体内抗肿瘤作用。

In vivo antitumor effects of unconjugated CD30 monoclonal antibodies on human anaplastic large-cell lymphoma xenografts.

作者信息

Tian Z G, Longo D L, Funakoshi S, Asai O, Ferris D K, Widmer M, Murphy W J

机构信息

Laboratory of Leukocyte Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.

出版信息

Cancer Res. 1995 Nov 15;55(22):5335-41.

PMID:7585597
Abstract

CD30 is a M(r) 120,000 surface antigen identified originally by the Ki-1 monoclonal antibody (moAb) against primary and cultured Reed-Sternberg cells present in Hodgkin's disease and anaplastic large-cell lymphomas (ALCLs). Examination of two ALCL cell lines (Karpas 299 and Michel) demonstrated cell surface expression of CD30. Incubation of these lymphomas with two anti-CD30 moAbs that recognize the ligand-binding site (M44 or HeFi-1) resulted in significant growth inhibition in vitro, with significant decreases in cell viability. Another anti-CD30 moAb, Ber-H2, which recognizes a determinant not involved in ligand binding, had no effect on ALCL growth in vitro. When these human ALCL lines were transferred i.v. into mice with severe combined immune deficiency, the mice developed extensive metastasis in the s.c., brain, or eye tissues. The treatment of mice with either M44 or HeFi-1 anti-CD30 moAbs resulted in significant increases in survival, with some mice remaining disease free for more than 100 days. Thus, anti-CD30 treatment is efficacious for CD30+ ALCL cell lines in vivo, and unconjugated anti-CD30 moAbs may be of potential clinical use.

摘要

CD30是一种分子量为120,000的表面抗原,最初由Ki-1单克隆抗体(moAb)鉴定,该抗体针对霍奇金病和间变性大细胞淋巴瘤(ALCL)中存在的原代和培养的里德-斯腾伯格细胞。对两种ALCL细胞系(Karpas 299和Michel)的检测显示了CD30的细胞表面表达。用两种识别配体结合位点的抗CD30 moAb(M44或HeFi-1)孵育这些淋巴瘤,导致体外显著的生长抑制,细胞活力显著下降。另一种抗CD30 moAb Ber-H2识别不参与配体结合的决定簇,对ALCL的体外生长没有影响。当将这些人ALCL细胞系静脉注射到严重联合免疫缺陷小鼠体内时,小鼠在皮下、脑或眼组织中发生广泛转移。用M44或HeFi-1抗CD30 moAb治疗小鼠可显著提高生存率,一些小鼠可无病存活超过100天。因此,抗CD30治疗对体内CD30+ ALCL细胞系有效,未偶联的抗CD30 moAb可能具有潜在的临床应用价值。

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