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卡妥索单抗联合活化T细胞可有效裂解耐化疗的上皮细胞黏附分子阳性三阴性乳腺癌细胞系。

Catumaxomab with Activated T-cells Efficiently Lyses Chemoresistant EpCAM-positive Triple-negative Breast Cancer Cell Lines.

作者信息

Kubo Makoto, Umebayashi Masayo, Kurata Kanako, Mori Hitomi, Kai Masaya, Onishi Hideya, Katano Mitsuo, Nakamura Masafumi, Morisaki Takashi

机构信息

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Fukuoka General Cancer Clinic, Fukuoka, Japan.

出版信息

Anticancer Res. 2018 Jul;38(7):4273-4279. doi: 10.21873/anticanres.12724.

Abstract

BACKGROUND/AIM: Epithelial cell adhesion molecule (EpCAM) is expressed in various types of cancer, including breast cancer, and is correlated with metastasis, invasion, therapeutic resistance and prognosis. Moreover, several cell surface markers, such as CD44 and EpCAM, are molecular targets on cancer stem-like cells of breast cancer. The aim of this study was to investigate whether catumaxomab, a clinical-grade bispecific antibody that binds to both EpCAM on tumor cells and CD3 on T-cells, combined with activated T-cells can eliminate chemoresistant triple-negative breast cancer (TNBC) cells in vitro.

MATERIALS AND METHODS

First, a cell line (MUK-BC1) was established from human breast carcinoma cells derived from a patient with chemoresistant and disseminated breast cancer. These EpCAM-positive TNBC cells were almost completely resistant to various drug-mediated cytotoxicities up to a concentration of 10 μg/ml.

RESULTS

Pre-treatment with catumaxomab and subsequent addition of interleukin-2/OKT3-activated autologous T-cells eliminated EpCAM-positive TNBC cells.

CONCLUSION

Catumaxomab combined with activated T-cells may be a potent therapeutic modality to overcome chemoresistant EpCAM-positive TNBC cells.

摘要

背景/目的:上皮细胞黏附分子(EpCAM)在包括乳腺癌在内的多种癌症类型中表达,且与转移、侵袭、治疗耐药性及预后相关。此外,几种细胞表面标志物,如CD44和EpCAM,是乳腺癌癌干细胞样细胞上的分子靶点。本研究的目的是调查卡妥索单抗(一种临床级双特异性抗体,可同时结合肿瘤细胞上的EpCAM和T细胞上的CD3)与活化T细胞联合使用是否能在体外消除化疗耐药的三阴性乳腺癌(TNBC)细胞。

材料与方法

首先,从一名患有化疗耐药性播散性乳腺癌患者的人乳腺癌细胞中建立了一个细胞系(MUK-BC1)。这些EpCAM阳性的TNBC细胞对浓度高达10μg/ml的各种药物介导的细胞毒性几乎完全耐药。

结果

先用卡妥索单抗预处理,随后添加白细胞介素-2/OKT3活化的自体T细胞可消除EpCAM阳性的TNBC细胞。

结论

卡妥索单抗与活化T细胞联合使用可能是克服化疗耐药的EpCAM阳性TNBC细胞的一种有效治疗方式。

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