López-Requena Alejandro, Mateo de Acosta Cristina, Pérez Alexis, Valle Aisel, Lombardero Josefa, Sosa Katya, Pérez Rolando, Vázquez Ana María
Department of Antibody Engineering, Center of Molecular Immunology, PO Box 16040, Havana 11600, Cuba.
Hybrid Hybridomics. 2003 Aug;22(4):235-43. doi: 10.1089/153685903322328965.
P3 monoclonal antibody (MAb) is a murine IgM that specifically recognizes N-glycolyl (NeuGc)-gangliosides and sulfatides. It also reacts with antigens expressed in human breast tumors and melanoma. In syngeneic model, P3 MAb is able to elicit a strong anti-idiotypic (Ab2) antibody response, even in the absence of adjuvants or carrier proteins. 1E10 MAb is an anti-idiotypic antibody specific for P3 MAb that has demonstrated anti-tumoral effects in syngeneic and allogeneic animals. Here we report the construction of the human IgG(1) chimeric P3 and 1E10 antibodies, and the evaluation of the maintenance of the main properties of the murine MAbs. Chimeric P3 antibody specifically reacted with GM3(NeuGc) and GM2(NeuGc) gangliosides, and not with their acetylated variants. Also, it strongly recognized the anti-idiotypic 1E10 MAb. Chimeric 1E10 antibody specifically reacted with P3 MAb. Upon immunization of Balb/c mice with both chimeric antibodies, we were able to demonstrate the immunodominance of their variable regions. The anti-idiotypic response induced by both antibodies was strong and in most of the mice was even significantly higher than the anti-isotypic response, despite the fact that 70% of the chimeric molecule is xenogenic with respect to the animal model.
P3单克隆抗体（MAb）是一种鼠源IgM，可特异性识别N-羟乙酰神经氨酸（NeuGc）-神经节苷脂和硫脂。它还与人类乳腺肿瘤和黑色素瘤中表达的抗原发生反应。在同基因模型中，即使没有佐剂或载体蛋白，P3单克隆抗体也能够引发强烈的抗独特型（Ab2）抗体反应。1E10单克隆抗体是一种针对P3单克隆抗体的抗独特型抗体，已在同基因和异基因动物中显示出抗肿瘤作用。在此，我们报告了人IgG(1)嵌合P3和1E10抗体的构建，以及对鼠源单克隆抗体主要特性维持情况的评估。嵌合P3抗体与GM3(NeuGc)和GM2(NeuGc)神经节苷脂特异性反应，而不与其乙酰化变体反应。此外，它能强烈识别抗独特型1E10单克隆抗体。嵌合1E10抗体与P3单克隆抗体特异性反应。在用两种嵌合抗体免疫Balb/c小鼠后，我们能够证明其可变区的免疫显性。尽管嵌合分子的70%相对于动物模型是异种的，但两种抗体诱导的抗独特型反应都很强，并且在大多数小鼠中甚至显著高于抗同种型反应。
