title: A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth and enhances NK cells-mediated tumor immunity.
abstract: Carcinoembryonic antigen (CEA, CEACAM5, and CD66e) has been found to be associated with various types of cancers, particularly colorectal carcinoma, and developed to be a molecular target for cancer diagnosis and therapy. In present study, we generated a novel anti-CEACAM5 monoclonal antibody, namely mAb CC4, by immunizing mice with living colorectal cancer LS174T cells. Immunohistochemical studies found that mAb CC4 specifically and strongly binds to tumor tissues, especially colorectal adenocarcinoma. In xenografted mice, mAb CC4 is specifically accumulated in tumor site and remarkably represses colorectal tumor growth. In vitro functional analysis showed that mAb CC4 significantly suppresses cell proliferation, migration and aggregation of colorectal cancer cells and also raises strong ADCC reaction. More interestingly, mAb CC4 is able to enhance NK cytotoxicity against MHC-I-deficient colorectal cancer cells by blocking intercellular interaction between epithelial CEACAM5 and NK inhibitory receptor CEACAM1. These data suggest that mAb CC4 has the potential to be developed as a novel tumor-targeting carrier and cancer therapeutic.
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Chaogu
authors: C
authors: Zheng
authors: Jing
authors: J
authors: Feng
authors: Di
authors: D
authors: Lu
authors: Ping
authors: P
authors: Wang
authors: Shu
authors: S
authors: Xing
authors: Jean-Luc
authors: JL
authors: Coll
authors: Dongling
authors: D
authors: Yang
authors: Xiyun
authors: X
authors: Yan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002449:Cell Aggregation; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology*; D018604:Epitope Mapping; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D002272:Carcinoembryonic Antigen