B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma.

Published

Journal Article

PURPOSE:Multiple myeloma is a usually incurable malignancy of plasma cells. New therapies are urgently needed for multiple myeloma. Adoptive transfer of chimeric antigen receptor (CAR)-expressing T cells is a promising new therapy for hematologic malignancies, but an ideal target antigen for CAR-expressing T-cell therapies for multiple myeloma has not been identified. B-cell maturation antigen (BCMA) is a protein that has been reported to be selectively expressed by B-lineage cells including multiple myeloma cells. Our goal was to determine if BCMA is a suitable target for CAR-expressing T cells. EXPERIMENTAL DESIGN:We conducted an assessment of BCMA expression in normal human tissues and multiple myeloma cells by flow cytometry, quantitative PCR, and immunohistochemistry. We designed and tested novel anti-BCMA CARs. RESULTS:BCMA had a restricted RNA expression pattern. Except for expression in plasma cells, BCMA protein was not detected in normal human tissues. BCMA was not detected on primary human CD34(+) hematopoietic cells. We detected uniform BCMA cell-surface expression on primary multiple myeloma cells from five of five patients. We designed the first anti-BCMA CARs to be reported and we transduced T cells with lentiviral vectors encoding these CARs. The CARs gave T cells the ability to specifically recognize BCMA. The anti-BCMA-CAR-transduced T cells exhibited BCMA-specific functions including cytokine production, proliferation, cytotoxicity, and in vivo tumor eradication. Importantly, anti-BCMA-CAR-transduced T cells recognized and killed primary multiple myeloma cells. CONCLUSIONS:BCMA is a suitable target for CAR-expressing T cells, and adoptive transfer of anti-BCMA-CAR-expressing T cells is a promising new strategy for treating multiple myeloma.

Full Text

Cited Authors

  • Carpenter, RO; Evbuomwan, MO; Pittaluga, S; Rose, JJ; Raffeld, M; Yang, S; Gress, RE; Hakim, FT; Kochenderfer, JN

Published Date

  • April 2013

Published In

Volume / Issue

  • 19 / 8

Start / End Page

  • 2048 - 2060

PubMed ID

  • 23344265

Pubmed Central ID

  • 23344265

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-12-2422

Language

  • eng