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Recombinant Human Monoclonal IgA Antibody Against CEA to Recruit Neutrophils to CEA-Expressing Cells

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Abstract:

IgA is able to trigger antibody-dependent cellular cytotoxicity (ADCC) by recruiting neutrophils expressing the Fc receptor for the CHα 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 CHα 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 45scFvLCHα, was purified from hemolymph by Ni-affinity chromatography and characterized by ELISA, Western blotting, and the ADCC assay. 45scFvLCHα with an IgA antigenicity was bound to CEA and showed effective killing of the CEA-expressing cells in the presence of IFN--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.

Keywords: Antibody-dependent cellular cytotoxicity (ADCC); Carcinoembryonic antigen (CEA); IgA; Immunotherapy; Neutrophils

Document Type: Research Article

DOI: https://doi.org/10.3727/096504008786111374

Publication date: 2008-05-01

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