title: Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor.
abstract: Donor lymphocyte infusions (DLIs) 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 B-cell maturation antigen (BCMA), a transmembrane receptor of the tumor necrosis factor (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 healthy 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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, M530, Boston, MA 02115, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bellucci
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Sabina
authors.initials: S
authors.lastname: Chiaretti
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Wu
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Zorn
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.forename: Bingyan
authors.initials: B
authors.lastname: Wu
authors.forename: Christine
authors.initials: C
authors.lastname: Canning
authors.forename: Robert
authors.initials: R
authors.lastname: Schlossman
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D053301:B-Cell Maturation Antigen; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D020350:Graft vs Tumor Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology* / Q000378:metabolism*; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D053301:B-Cell Maturation Antigen; D018124:Receptors, Tumor Necrosis Factor; C086966:TNFRSF17 protein, human