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Bu DX, Singh R, Choi EE, et al. Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma. Oncotarget. 2018;9(40):25764-25780doi: 10.18632/oncotarget.25359.
Bu, D. X., Singh, R., Choi, E. E., Ruella, M., Nunez-Cruz, S., Mansfield, K. G., Bennett, P., Barton, N., Wu, Q., Zhang, J., Wang, Y., Wei, L., Cogan, S., Ezell, T., Joshi, S., Latimer, K. J., Granda, B., Tschantz, W. R., Young, R. M., Huet, H. A., Richardson, C. J., & Milone, M. C. (2018). Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma. Oncotarget, 9(40), 25764-25780. https://doi.org/10.18632/oncotarget.25359
Bu, De-Xiu, et al. "Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma." Oncotarget vol. 9,40 (2018): 25764-25780. doi: https://doi.org/10.18632/oncotarget.25359
Bu DX, Singh R, Choi EE, Ruella M, Nunez-Cruz S, Mansfield KG, Bennett P, Barton N, Wu Q, Zhang J, Wang Y, Wei L, Cogan S, Ezell T, Joshi S, Latimer KJ, Granda B, Tschantz WR, Young RM, Huet HA, Richardson CJ, Milone MC. Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma. Oncotarget. 2018 May 25;9(40):25764-25780. doi: 10.18632/oncotarget.25359. eCollection 2018 May 25. PMID: 29899820; PMCID: PMC5995247.
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Oncotarget. 2018 May 25;9(40):25764-25780. doi: 10.18632/oncotarget.25359. eCollection 2018 May 25.

Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma.

Oncotarget

De-Xiu Bu, Reshma Singh, Eugene E Choi, Marco Ruella, Selene Nunez-Cruz, Keith G Mansfield, Paul Bennett, Nathanial Barton, Qilong Wu, Jiquan Zhang, Yongqiang Wang, Lai Wei, Shawn Cogan, Tucker Ezell, Shree Joshi, Kellie J Latimer, Brian Granda, William R Tschantz, Regina M Young, Heather A Huet, Celeste J Richardson, Michael C Milone

Affiliations

  1. Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
  2. Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
  3. China Novartis Institutes for Biomedical Research, Shanghai 201203, China.
  4. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

PMID: 29899820 PMCID: PMC5995247 DOI: 10.18632/oncotarget.25359

Abstract

Multiple myeloma has a continued need for more effective and durable therapies. B cell maturation antigen (BCMA), a plasma cell surface antigen and member of the tumor necrosis factor (TNF) receptor superfamily, is an attractive target for immunotherapy of multiple myeloma due to its high prevalence on malignant plasma cells. The current work details the pre-clinical evaluation of BCMA expression and development of a chimeric antigen receptor (CAR) targeting this antigen using a fully human single chain variable fragment (scFv). We demonstrate that BCMA is prevalently, but variably expressed by all MM with expression on 25-100% of malignant plasma cells. Extensive Immunohistochemical analysis of normal tissue expression using commercially available polyclonal antibodies demonstrated expression within B-lineage cells across a number of tissues as expected. Based upon the highly restricted expression of BCMA within normal tissues, we generated a set of novel, fully human scFv binding domains to BCMA by screening a naïve B-cell derived phage display library. Using a series of

Keywords: BCMA; CAR; T cell; multiple myeloma

Conflict of interest statement

CONFLICTS OF INTEREST E.D.C, R.S., Q. W., J.Z., Y. W., L.W., A.L., S.C., T.E., S. J., K.G. M., K.J.L., W.R.T., H.A.H, DX. B., P.B., N.B., and C.J.R. were paid employees of Novartis at the time this wo

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