Homodimers but not monomers of Rituxan (chimeric anti-CD20) induce apoptosis in human B-lymphoma cells and synergize with a chemotherapeutic agent and an immunotoxin
Homodimers but not monomers of Rituxan (chimeric anti-CD20) induce apoptosis in human B-lymphoma cells and synergize with a chemotherapeutic agent and an immunotoxin
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DOI：
10.1182/blood.v97.5.1392
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发表时间：
2001-03-01
期刊：
影响因子：
20.3
通讯作者：
Vitetta, ES
中科院分区：
文献类型：
--
作者：
Ghetie, MA;Bright, H;Vitetta, ES
1997年，嵌合抗CD 20单克隆抗体（mAb）（Rituxan）被批准用于治疗低度/滤泡性B细胞淋巴瘤。利妥昔单抗具有半衰期长、免疫原性低的特点，并可介导效应子功能，在体外可诱导肿瘤细胞凋亡。先前对与肿瘤性B细胞反应的mAb的研究表明，免疫球蛋白G的同源二聚体（[IgG]（2））通常比其单体（IgG）（1）对应物更有效地抑制细胞生长。在本研究中，比较了IgG或F（ab '）（2）同源二聚体与Rituxan单体在体外抑制几种不同B淋巴瘤细胞系生长的能力。发现Rituxan的同源二聚体在体外具有上级的抗生长活性，并且F（ab '）2同源二聚体的活性最高。Rituxan的同源二聚体（而不是单体）在体外诱导了几种B细胞淋巴瘤细胞系的凋亡和坏死;细胞生长的抑制不依赖于Fc受体的存在或靶细胞上CD 20密度的10倍或更大差异。与单体相比，Rituxan同源二聚体也使耐药的CD 20（+）B淋巴瘤细胞对化疗药物更敏感，并在体外与抗CD 22免疫毒素协同作用。（血液，2001;97：1392-1398）（C）2001年由美国血液学会。
In 1997, a chimeric anti-CD20 monoclonal antibody (mAb) (Rituxan) was approved for the treatment of low-grade/follicular B-cell lymphoma. Rituxan has a long half-life and low immunogenicity, and it mediates effector function, Rituxan induces apoptosis in some tumor cell lines in vitro. Previous studies with mAbs that react with neoplastic B cells have demonstrated that homodimers of immunoglobulin G ([IgG](2)) often inhibit cell growth more effectively than their monomeric (IgG)(1) counterparts. In this study, the ability of IgG or F(ab')(2) homodimers vs monomers of Rituxan were compared for their ability to inhibit the growth of several different B-lymphoma cell lines in vitro. It was found that homodimers of Rituxan had superior antigrowth activity in vitro and that F(ab')2 homodimers were the most active. Homodimers, but not monomers, of Rituxan induced both apoptosis and necrosis of several B-cell lymphoma lines in vitro; the inhibition of cell growth was not dependent upon the presence of Fc receptors or upon 10-fold or greater differences in the density of CD20 on the target cells. Rituxan homodimers, compared with monomers, also rendered drug-resistant CD20(+) B-lymphoma cells more sensitive to chemotherapeutic agents and synergized with an anti-CD22 immunotoxin in vitro. (Blood, 2001;97: 1392-1398) (C) 2001 by The American Society of Hematology.