Immunogenicity of bone morphogenetic proteins.
OBJECTIVE
The object of this paper is to review the immunogenicity of bone morphogenetic proteins (BMPs) and to compare the results of the immunogenicity characterization and clinical consequences between recombinant human (rh)BMP-2 and recombinant human osteogenic protein-1 (rhOP-1/BMP-7).


METHODS
The immunogenicity of therapeutic proteins and its clinical effects were reviewed. The characteristics of BMPs were also described in terms of immunogenicity. The methods and results of antibody detection in various clinical trials of rhBMP-2 and rhOP-1 were compared, including the most recent studies using a systematic characterization strategy with both a binding assay and bioassay.


RESULTS
Similar to all recombinant human proteins, rhBMPs induce immune responses in a select subgroup of patients. Adverse effects from this response in these patients, however, have not been reported with antibody formation to either rhBMP-2 or rhOP-1. Overall, the incidence of antibody formation was slightly higher in rhOP-1 trials than in rhBMP-2 trials.


CONCLUSIONS
Although they occur in a subgroup of patients, the immune responses against rhBMPs have no correlation with any clinical outcome or safety parameter. Clinicians, however, must be aware of the potential complications caused by the immunogenicity of BMPs until more studies clearly elucidate their safety.
Department of Orthopaedic Surgery, Thomas Jefferson University and The Rothman Institute, Philadelphia, PA 19107, USA.
Chang Ju
CJ
Hwang
Alexander R
AR
Vaccaro
James P
JP
Lawrence
Joseph
J
Hong
Huub
H
Schellekens
Moulay Hicham
MH
Alaoui-Ismaili
Dean
D
Falb
D000917:Antibody Formation; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7 / Q000276:immunology; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D006801:Humans; D011994:Recombinant Proteins / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2