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Cancers 2018, 10(9), 323; https://doi.org/10.3390/cancers10090323

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

1
ProMab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA
2
Forevertek Biotechnology Co., Ltd., Building M0, Oversea Graduate Park National High-Tech Industrial Zone, Changsha 410003, China
*
Author to whom correspondence should be addressed.
Received: 27 July 2018 / Revised: 31 August 2018 / Accepted: 4 September 2018 / Published: 11 September 2018
(This article belongs to the Special Issue CAR-T Cell Therapy-Novel Approaches and Challenges)
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Abstract

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-γ in vitro. BCMA-dependent cytotoxicity and IFN-γ 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. View Full-Text
Keywords: chimeric antigen receptor; CAR-T cells; multiple myeloma; immunotherapy; cell therapy; tumor antigen; cancer; xenograft chimeric antigen receptor; CAR-T cells; multiple myeloma; immunotherapy; cell therapy; tumor antigen; cancer; xenograft
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Berahovich, R.; Zhou, H.; Xu, S.; Wei, Y.; Guan, J.; Guan, J.; Harto, H.; Fu, S.; Yang, K.; Zhu, S.; Li, L.; Wu, L.; Golubovskaya, V. CAR-T Cells Based on Novel BCMA Monoclonal Antibody Block Multiple Myeloma Cell Growth. Cancers 2018, 10, 323.

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