Murine monoclonal anti-idiotypic antibody as a surrogate antigen for humanHer-2/neu

The anti-idiotypic (1d) monoclonal antibody (MAb) 520C9-6b (1gG1k), raised in syngenic mice against the murine anti Her2/neu MAb 520C9 (Ab1), function ally mimics a human Her2/neu epitope and serves as a surrogate for the prot ein antigen. Immunization of allogeneic C57BL/6 mice and rabbits with 520C9 -6b (Ab2) induced anti-Her2/neu-specific antibodies that react with antigen -positive SKBr3 cells by ELISA and FAGS analysis. The immune sera inhibited binding between Ab I and Ab2 and vice verse (binding of Ab2 to Abl), indic ating that it was a true anti-anti-id (Ab3) antibody. The Ab3 sera or purif ied Ab3 specifically lysed Her2/ neu-positive SKBr3 cells, but no significa nt lysis was observed in antigen negative LS174T cells in an antibody depen dent cellular cytotoxicity assay. An 1d-specific cellular immune response w as also demonstrated in an in vitro lymphocyte proliferation assay. Further more, a panel of tumor tissues and tumor cells was screened for the presenc e of the Her2/ neu epitope by its reactivity with Ab1 and Ab3 using immunoh istochemistry and FAGS analysis. Identical results were obtained using eith er Ab1 or Ab3 (Ab 1'). The data indicated that anti-id 520C9-6b can induce Her2/neu-specific antibody in experimental animals and may serve as a poten tial network antigen for the treatment of patients bearing Her2/neu-positiv e tumors. (C) 2001 Wiley-Liss, Inc.