Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose.
BACKGROUND
Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, is approved for use in colorectal cancer and squamous-cell carcinoma of the head and neck. A high prevalence of hypersensitivity reactions to cetuximab has been reported in some areas of the United States.


METHODS
We analyzed serum samples from four groups of subjects for IgE antibodies against cetuximab: pretreatment samples from 76 case subjects who had been treated with cetuximab at multiple centers, predominantly in Tennessee, Arkansas, and North Carolina; samples from 72 control subjects in Tennessee; samples from 49 control subjects with cancer in northern California; and samples from 341 female control subjects in Boston.


RESULTS
Among 76 cetuximab-treated subjects, 25 had a hypersensitivity reaction to the drug. IgE antibodies against cetuximab were found in pretreatment samples from 17 of these subjects; only 1 of 51 subjects who did not have a hypersensitivity reaction had such antibodies (P<0.001). IgE antibodies against cetuximab were found in 15 of 72 samples (20.8%) from control subjects in Tennessee, in 3 of 49 samples (6.1%) from northern California, and in 2 of 341 samples (0.6%) from Boston. The IgE antibodies were shown to be specific for an oligosaccharide, galactose-alpha-1,3-galactose, which is present on the Fab portion of the cetuximab heavy chain.


CONCLUSIONS
In most subjects who had a hypersensitivity reaction to cetuximab, IgE antibodies against cetuximab were present in serum before therapy. The antibodies were specific for galactose-alpha-1,3-galactose.
Chung
Christine H
CH
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, USA.
Mirakhur
Beloo
B
Chan
Emily
E
Le
Quynh-Thu
QT
Berlin
Jordan
J
Morse
Michael
M
Murphy
Barbara A
BA
Satinover
Shama M
SM
Hosen
Jacob
J
Mauro
David
D
Slebos
Robbert J
RJ
Zhou
Qinwei
Q
Gold
Diane
D
Hatley
Tina
T
Hicklin
Daniel J
DJ
Platts-Mills
Thomas A E
TA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000707:Anaphylaxis / Q000139:chemically induced* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D016022:Case-Control Studies; D000068818:Cetuximab; D003429:Cross Reactions; D004187:Disaccharides / Q000276:immunology*; D000939:Epitopes; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004187:Disaccharides; D000939:Epitopes; C055075:galactosyl-(1-3)galactose; D007073:Immunoglobulin E; D066246:ErbB Receptors; D000068818:Cetuximab