CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy Journal Article

Authors: Zhou, P.; Comenzo, R. L.; Olshen, A. B.; Bonvini, E.; Koenig, S.; Maslak, P. G.; Fleisher, M.; Hoffman, J.; Jhanwar, S.; Young, J. W.; Nimer, S. D.; Boruchov, A. M.
Article Title: CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy
Abstract: Despite advances in therapy, many patients with systemic light-chain amyloidosis (AL) die within 3 years from diagnosis. The humanized 2B6 monoclonal antibody (MoAb) is specific for the low-affinity IgG Fc receptor CD32B and effective in a human CD32B+ B-cell lymphoma murine xenograft model. Because MoAb therapy could improve outcomes in AL, we studied CD32B expression by clonal plasma cells obtained from 48 patients with AL. Transcript profiling showed that expression of CD32B was significantly higher than expression of all other Fc receptor family members. Reverse-transcriptase polymerase chain reaction (RT-PCR) using double-enriched CD138+ plasma cells showed uniform expression of the stable cell surface CD32B1 isoform at diagnosis and relapse, and flow cytometry showed intense CD32B cell surface staining on 99% of CD138+ plasma cells at diagnosis and relapse. These data provide a rationale for the novel therapeutic targeting of CD32B using the humanized 2B6 MoAb in patients with systemic AL-amyloidosis. © 2008 by The American Society of Hematology.
Keywords: adult; clinical article; controlled study; aged; aged, 80 and over; middle aged; unclassified drug; lenalidomide; thalidomide; nonhuman; drug megadose; flow cytometry; antigen expression; mouse; animal; metabolism; animals; mice; reverse transcription polymerase chain reaction; bortezomib; gene expression profiling; animal experiment; animal model; relapse; recurrence; dexamethasone; melphalan; amyloidosis; autologous stem cell transplantation; drug screening; xenograft model antitumor assays; monoclonal antibody; gene expression regulation; b cell lymphoma; plasma cell; lymphoma, b-cell; membrane antigen; biosynthesis; immunology; antibodies, monoclonal; xenograft; reverse transcriptase polymerase chain reaction; recurrent disease; fc receptor; receptors, igg; antigens, cd; cell clone; fc receptor iib; immunoglobulin light chain; immunoglobulin light chains; leukocyte antigen; plasma cells; antibody affinity; syndecan 1; systemic light chain amyloidosis; monoclonal antibody 2b6; sdc1 protein, human; syndecan-1
Journal Title: Blood
Volume: 111
Issue: 7
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2008-04-01
Start Page: 3403
End Page: 3406
Language: English
DOI: 10.1182/blood-2007-11-125526
PUBMED: 18216299
PROVIDER: scopus
PMCID: PMC2275009
Notes: --- - "Cited By (since 1996): 12" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Raymond L Comenzo
    111 Comenzo
  2. Ping Zhou
    43 Zhou
  3. James Edward Hoffman
    10 Hoffman
  4. Adam B Olshen
    107 Olshen
  5. Stephen D Nimer
    336 Nimer
  6. James W Young
    246 Young
  7. Peter Maslak
    160 Maslak
  8. Martin Fleisher
    228 Fleisher
  9. Suresh C Jhanwar
    204 Jhanwar