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抗CD26单克隆抗体1F7对人CD30 + 间变性大细胞T细胞淋巴瘤Karpas 299的体外和体内抗肿瘤作用

In vitro and in vivo antitumor effect of the anti-CD26 monoclonal antibody 1F7 on human CD30+ anaplastic large cell T-cell lymphoma Karpas 299.

作者信息

Ho L, Aytac U, Stephens L C, Ohnuma K, Mills G B, McKee K S, Neumann C, LaPushin R, Cabanillas F, Abbruzzese J L, Morimoto C, Dang N H

机构信息

Department of Gastrointestinal Oncology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Clin Cancer Res. 2001 Jul;7(7):2031-40.

Abstract

CD26 is a M(r) 110,000 surface glycoprotein with diverse functional properties, including having a potentially significant role in tumor development, and antibodies to CD26 mediate pleomorphic cellular functions. In this report, we show that binding of soluble anti-CD26 monoclonal Ab 1F7 inhibits the growth of the human CD30+ anaplastic large cell T-cell lymphoma cell line Karpas 299 in both in vitro and in vivo experiments. In vitro experiments show that 1F7 induces cell cycle arrest at the G1-S checkpoint, associated with enhanced p21 expression that is dependent on de novo protein synthesis. Furthermore, experiments with a severe combined immunodeficient mouse tumor model demonstrate that 1F7 treatment significantly enhances survival of tumor-bearing mice by inhibiting tumor formation. Our data therefore suggest that anti-CD26 treatment may have potential clinical use for CD26+ hematological malignancies.

摘要

CD26是一种分子量为110,000的表面糖蛋白,具有多种功能特性,包括在肿瘤发展中可能发挥重要作用,并且针对CD26的抗体介导多种细胞功能。在本报告中,我们表明可溶性抗CD26单克隆抗体1F7的结合在体外和体内实验中均抑制人CD30 +间变性大细胞T细胞淋巴瘤细胞系Karpas 299的生长。体外实验表明,1F7诱导细胞周期在G1-S检查点停滞,这与依赖于从头蛋白质合成的p21表达增强有关。此外,使用严重联合免疫缺陷小鼠肿瘤模型的实验表明,1F7治疗通过抑制肿瘤形成显著提高荷瘤小鼠的存活率。因此,我们的数据表明抗CD26治疗可能对CD26 +血液系统恶性肿瘤具有潜在的临床应用价值。

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