Shared antigenic epitopes and pathobiological functions of anti-p185(her2/neu) monoclonal antibodies.
We have studied two anti-p185 antibodies: the monoclonal antibody 7. 16.4 and rhuMAb 4D5, which were raised against the the ectodomain of rat (p185(neu)), and the human (p185(her2/neu)) homolog, respectively. Studies on the structure of these two antibodies indicate that they share structural similarity in the variable region, especially the CDR3 region, which determines the antibody-antigen interaction. Further studies by flow cytometry revealed that 7.16.4 can compete with rhuMAb4D5 for binding to the cell surface p185(her2/neu), suggesting that these two antibodies share an epitope on the p185 receptor. Furthermore, 7.16.4 can also inhibit proliferation and transformation caused by p185(her2/neu). Moreover the rhuMAb 4D5 binds to the rat p185(neu). With the observation that 7.16.4 positively stains human breast cancer tissues that overexpress p185(her2/neu), 7.16.4 may be useful for the pathological diagnosis and therapy of human tumors.
Zhang
H
H
Department of Pathology, School of Medicine, University of Pennsylvania, 36th Hamilton Walk, Philadelphia, Pennsylvania 19104, USA.
Wang
Q
Q
Montone
K T
KT
Peavey
J E
JE
Drebin
J A
JA
Greene
M I
MI
Murali
R
R
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000502:physiology*; D061067:Antibodies, Monoclonal, Humanized; D001666:Binding Sites, Antibody; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D018719:Erb-b2 Receptor Tyrosine Kinases; D013778:Tetrazolium Salts; D013844:Thiazoles; D000068878:Trastuzumab; C022616:thiazolyl blue