CAR-T Cells Based on Novel BCMA Monoclonal Antibody Block Multiple Myeloma Cell Growth

被引：26

作者：

Berahovich, Robert ^{[1
]}

Zhou, Hua ^{[1
]}

Xu, Shirley ^{[1
]}

Wei, Yuehua ^{[1
]}

Guan, Jasper ^{[1
]}

Guan, Jian ^{[1
]}

Harto, Hizkia ^{[1
]}

Fu, Shuxiang ^{[2
]}

Yang, Kaihuai ^{[2
]}

Zhu, Shuying ^{[2
]}

Li, Le ^{[1
,2
]}

Wu, Lijun ^{[1
]}

Golubovskaya, Vita ^{[1
]}

机构：

[1] ProMab Biotechnol, 2600 Hilltop Dr, Richmond, CA 94806 USA

[2] Forevertek Biotechnol Co Ltd, Oversea Grad Pk Natl High Tech Ind Zone, Bldg M0, Changsha 410003, Hunan, Peoples R China

来源：

CANCERS | 2018年 / 10卷 / 09期

关键词：

chimeric antigen receptor; CAR-T cells; multiple myeloma; immunotherapy; cell therapy; tumor antigen; cancer; xenograft; CHIMERIC ANTIGEN RECEPTORS; MATURATION ANTIGEN; IMMUNOTHERAPY; APRIL; MALIGNANCIES; REDIRECTION; THERAPY; TARGET; BAFF; TACI;

D O I：

10.3390/cancers10090323

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The cell-surface protein B cell maturation antigen (BCMA, CD269) has emerged as a promising target for CAR-T cell therapy for multiple myeloma. In order to create a novel BCMA CAR, we generated a new BCMA monoclonal antibody, clone 4C8A. This antibody exhibited strong and selective binding to human BCMA. BCMA CAR-T cells containing the 4C8A scFv were readily detected with recombinant BCMA protein by flow cytometry. The cells were cytolytic for RPMI8226, H929, and MM1S multiple myeloma cells and secreted high levels of IFN-gamma in vitro. BCMA-dependent cytotoxicity and IFN-gamma secretion were also observed in response to CHO (Chinese Hamster Ovary)-BCMA cells but not to parental CHO cells. In a mouse subcutaneous tumor model, BCMA CAR-T cells significantly blocked RPMI8226 tumor formation. When BCMA CAR-T cells were given to mice with established RPMI8226 tumors, the tumors experienced significant shrinkage due to CAR-T cell activity and tumor cell apoptosis. The same effect was observed with 3 humanized BCMA-CAR-T cells in vivo. These data indicate that novel CAR-T cells utilizing the BCMA 4C8A scFv are effective against multiple myeloma and warrant future clinical development.

引用

页数：16

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