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一种感染了爱泼斯坦-巴尔病毒的淋巴母细胞系(D430B),它在重症联合免疫缺陷小鼠体内生长,具有CD30 +间变性大细胞淋巴瘤的形态学特征,并且对抗CD30免疫毒素敏感。

An Epstein-Barr virus-infected lymphoblastoid cell line (D430B) that grows in SCID-mice with the morphologic features of a CD30+ anaplastic large cell lymphoma, and is sensitive to anti-CD30 immunotoxins.

作者信息

Tazzari P L, de Totero D, Bolognesi A, Testoni N, Pileri S, Roncella S, Reato G, Stein H, Gobbi M, Stirpe F

机构信息

Servizio di Immunoematologia e Trasfusionale, Policlinico S.Orsola, Bologna, Italy.

出版信息

Haematologica. 1999 Nov;84(11):988-95.

Abstract

BACKGROUND AND OBJECTIVE

In this study we describe a newly established CD30+ Epstein Barr virus (EBV)-infected B cell line derived from an EBV-infected B cell culture (utilized, once irradiated, as a feeder) which showed a B clonal rearrangement and strong CD30 antigen expression.

DESIGN AND METHODS

The cells injected into SCID mice were able to grow giving rise to CD30+ solid tumors with the morphologic features of an anaplastic large cell lymphoma (ALCL). Thus we tried to establish a model to investigate the potency of immunoconjugates containing a CD30 monoclonal antibody (Ber-H2) and ribosome-inactivating proteins (saporin, momordin and ricin A-chain) as toxic moieties.

RESULTS

We observed a strong cytotoxic activity of the anti-CD30 immunotoxins on the in vitro growth of D430B cells. High levels of anti-tumor activity were also observed in vivo, in the SCID mouse model.

INTERPRETATION AND CONCLUSIONS

The antitumor immunotoxin therapy was sccessful in our chosen animal model, the effecacy seeming to be associated with strength of CD30 expression. Our data suggest that immunotoxins should be tested (before use) on the tumor cells of the subject to be treated and that immunotoxins should be directed to different tumor-associated antigens to avoid selection of cell populations with different antigenic mosaics.

摘要

背景与目的

在本研究中,我们描述了一种新建立的CD30+爱泼斯坦-巴尔病毒(EBV)感染的B细胞系,其源自EBV感染的B细胞培养物(经照射后用作饲养细胞),该细胞系显示出B细胞克隆重排并强烈表达CD30抗原。

设计与方法

将这些细胞注射到SCID小鼠体内后能够生长,形成具有间变性大细胞淋巴瘤(ALCL)形态学特征的CD30+实体瘤。因此,我们试图建立一个模型来研究含有CD30单克隆抗体(Ber-H2)和核糖体失活蛋白(皂草素、苦瓜素和蓖麻毒素A链)作为毒性部分的免疫缀合物的效力。

结果

我们观察到抗CD30免疫毒素对D430B细胞的体外生长具有强烈的细胞毒活性。在SCID小鼠模型的体内实验中也观察到了高水平的抗肿瘤活性。

解读与结论

在我们选择的动物模型中,抗肿瘤免疫毒素治疗取得了成功,其疗效似乎与CD30表达的强度有关。我们的数据表明,免疫毒素在使用前应在待治疗对象的肿瘤细胞上进行检测,并且免疫毒素应针对不同的肿瘤相关抗原,以避免选择具有不同抗原镶嵌的细胞群体。

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