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  • Title: Recombinant human monoclonal igA antibody against CEA to recruit neutrophils to CEA-expressing cells.
    Author: Zhao J, Kuroki M, Shibaguchi H, Wang L, Huo Q, Takami N, Tanaka T, Kinugasa T, Kuroki M.
    Journal: Oncol Res; 2008; 17(5):217-22. PubMed ID: 18980018.
    Abstract:
    IgA is able to trigger antibody-dependent cellular cytotoxicity (ADCC) by recruiting neutrophils expressing the Fc receptor for the CHalpha chain. We herein describe the preparation of a human recombinant anti-CEA IgA antibody to kill carcinoembryonic antigen (CEA)-expressing tumor cells via ADCC by neutrophils. A single chain Fv (scFv) gene was constructed using a cDNA library of a hybridoma clone that produces a human anti-CEA monoclonal IgG4 (C2-45). The scFv gene, linked with a CHalpha gene, was inserted into the pBK283 vector, which was cotransfected into BmN4 insect cells with the wild-virus BmNPV. After cloning and amplification, the recombinated virus was injected into silkworm larvae. The resulting human recombinant IgA, designated as 45scFvLCHalpha, was purified from hemolymph by Ni-affinity chromatography and characterized by ELISA, Western blotting, and the ADCC assay. 45scFvLCHalpha with an IgA antigenicity was bound to CEA and showed effective killing of the CEA-expressing cells in the presence of IFN-gamma-activated neutrophils. These data suggest the recombinant anti-CEA IgA antibody recruiting neutrophils maybe a useful means for the antibody-based immunotherapy of human CEA-expressing tumors.
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