Recombinant Human Monoclonal IgA Antibody Against CEA to Recruit Neutrophils to CEA-Expressing Cells
| Autor: | Lin Wang, Tetsushi Kinugasa, Noboru Takami, Qun Huo, Toshihiro Tanaka, Masahide Kuroki, Motomu Kuroki, Jun Zhao, Hirotomo Shibaguchi |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Antigenicity Neutrophils medicine.drug_class Immunoglobulin Variable Region Fc receptor CHO Cells Monoclonal antibody law.invention Interferon-gamma Cricetulus Carcinoembryonic antigen law Cell Line Tumor Cricetinae medicine Animals Humans Immunoglobulin Fragments Antibody-dependent cell-mediated cytotoxicity biology Antibody-Dependent Cell Cytotoxicity Antibodies Monoclonal General Medicine Bombyx Virology Molecular biology Recombinant Proteins Carcinoembryonic Antigen Immunoglobulin A Oncology Monoclonal biology.protein Recombinant DNA Electrophoresis Polyacrylamide Gel Immunotherapy Antibody |
| Zdroj: | Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics. 17:217-222 |
| ISSN: | 0965-0407 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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