CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy.
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.
Zhou
Ping
P
Sloan-Kettering Institute, Department of Medicine, New York, NY 10021, USA.
Comenzo
Raymond L
RL
Olshen
Adam B
AB
Bonvini
Ezio
E
Koenig
Scott
S
Maslak
Peter G
PG
Fleisher
Martin
M
Hoffman
James
J
Jhanwar
Suresh
S
Young
James W
JW
Nimer
Stephen D
SD
Boruchov
Adam M
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007147:Immunoglobulin Light Chains; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000276:immunology; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1 / Q000276:immunology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D007147:Immunoglobulin Light Chains; D017452:Receptors, IgG; C508241:SDC1 protein, human; D053668:Syndecan-1