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B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma

B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma

Robert O Carpenter, Moses O Evbuomwan, Stefania Pittaluga, Jeremy J Rose, Mark Raffeld, Shicheng Yang, Ronald E Gress, Frances T Hakim, James N Kochenderfer

Clin Cancer Res. 2013 Apr 15;19(8):2048-60.

PMID: 23344265

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248878	BCMA human			Price

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