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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3945-3950.
Prepublished online as a Blood First Edition Paper on February 3, 2005; DOI 10.1182/blood-2004-11-4463.
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Submitted November 23, 2004
Accepted January 24, 2005
Graft versus tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma cell membrane receptor
Roberto Bellucci, Edwin P Alyea, Sabina Chiaretti, Catherine J Wu, Emmanuel Zorn, Edie Weller, Bingyan Wu, Christine Canning, Robert Schlossman, Nikhil C Munshi, Kenneth C Anderson, and Jerome Ritz*
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
Department of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, USA
* Corresponding author; email: Jerome_Ritz{at}dfci.Harvard.edu.
Donor lymphocyte infusions (DLI) induce effective graft versus tumor responses in patients with multiple myeloma who relapse after allogeneic hematopoietic stem cell transplantation. The graft-versus-myeloma response is presumably mediated primarily by donor T cells, but recent studies have also demonstrated the presence of antibodies specific for a variety of myeloma-associated antigens in patients who achieve complete remission after DLI. One of the B cell antigens identified in these studies was BCMA, a transmembrane receptor of the TNF superfamily that is selectively expressed by mature B cells. The present studies were undertaken to characterize the functional significance of antibodies to BCMA in vivo. Using transfected cells expressing BCMA, antibodies in patient serum were found to react with the cell surface domain of BCMA. Post-DLI patient serum was able to induce complement-mediated lysis and antibody dependent cellular cytotoxicity (ADCC) of transfected cells and primary myeloma cells expressing BCMA. BCMA antibodies were only found in post-DLI responders and not in other allogeneic transplant patients or normal donors. These results demonstrate that BCMA is a target of donor B cell immunity in patients with myeloma who respond to DLI. Antibody responses to cell surface BCMA may contribute directly to tumor rejection in vivo.
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