Immunohistochemical recognition of the epidermal growth factor receptor by the h-R3 antibody in the skin of experimental animals.
The h-R3 is a humanized monoclonal antibody (Mab) that binds to the external domain of the human epidermal growth factor receptor (EGF-R). It has being used for the treatment of head and neck tumors. Since it is known that different animal species have different EGF-R amino acid sequences, it raises the handicap that, a priori, the animal species relevant for the pharmacodynamic, pharmacokinetic, and toxicologic studies of this Mab are unknown. To elucidate relevant laboratory animal species, the authors investigated the immunohistochemical recognition by h-R3 Mab of EGF-R in small skin biopsy samples obtained from NMRI nu/nu, C57Bl/6, and OF-1 mice; Sprague-Dawley rats; Hartley guinea pigs; New Zealand rabbits; and Cercopithecus aethiops and Macaca fascicularis monkeys. Additionally, three human skin biopsies were obtained from trauma victims. The immunolocalization of EGF-R in different tissue sections was performed using the avidin-biotin peroxidase complex (ABC) technique. The skin sections from different tissues were tested with the biotinylated h-R3 Mab or with a biotinylated irrelevant Mab, used as negative control. The staining intensity was qualified as:-, no staining; +, weak staining; ++, moderate staining; +++, strong staining. Macaca fascicularis monkey, New Zealand rabbit, and OF-1 mouse skins had a strong staining intensity; Cercopithecus aethiops monkey and Sprague-Dawley rat skins showed a moderate to strong staining intensity; C57Bl/6 mouse skins showed a moderate staining intensity. No staining was observed in the skins from Hartley guinea pigs and MNRI nu/nu mice. The fact that h-R3 Mab recognizes other animal EGF receptors in addition to the human EGF-R makes it possible to perform relevant pharmacodynamic, pharmacokinetic, and toxicologic studies in some laboratory animals.
Maceira
Maura
M
Center for Molecular Immunology, Havana, Cuba.
Rengifo
Enrique
E
Cedeño
Mercedes
M
Merino
Nelson
N
Casacó Parada
Angel
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002522:Chlorocebus aethiops; D066246:ErbB Receptors / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D051379:Mice; D008819:Mice, Nude; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors