A mouse/human-chimeric bispecific antibody reactive with human carcinoembryonic antigen-expressing cells and human T-lymphocytes. 1996

M Kuwahara, and M Kuroki, and F Arakawa, and T Senba, and Y Matsuoka, and T Hideshima, and Y Yamashita, and H Kanda
First Department of Biochemistry, School of Medicine, Fukuoka University, Japan.

A mouse/human-chimeric bispecific antibody, designated CBA-CEACD3, with dual specificities for carcinoembryonic antigen (CEA) and CD3, was generated by chemical cross-linking of a chimeric antibody specific for CEA to another chimeric antibody against CD3. Flow cytometric analysis showed that CBA-CEACD3 can bind specifically to cells expressing CEA and to normal human peripheral blood mononuclear cells (HPBMCs) bearing CD3, respectively. Furthermore, a cell to cell adhesion analysis by a colorimetric assay using the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) demonstrated that CBA-CEACD3 is able to bind CEA-producing cells to CD3-expressing cells, suggesting that both arms of CBA-CEACD3 are simultaneously working and can retarget T-cells to the tumor. In an additional colorimetric assay using MTT, this antibody was shown to effectively mediate CEA-expressing tumor cell killing by freshly isolated HPBMCs. Together these results demonstrate that this chimeric bispecific antibody may serve as a potentially useful immunotherapeutic reagent for human CEA-producing cancers.

UI MeSH Term Description Entries
D002272 Carcinoembryonic Antigen A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment. Antigens, CD66e,CD66e Antigen,Antigen, CD66e,Antigen, Carcinoembryonic,CD66e Antigens
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D017252 CD3 Complex Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA). Antigens, CD3,CD3 Antigens,T3 Antigens,CD3 Antigen,T3 Antigen,T3 Complex,Antigen, CD3,Antigen, T3,Antigens, T3
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018033 Antibodies, Bispecific Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors. Bifunctional Antibodies,Bispecific Antibodies,Bispecific Monoclonal Antibodies,Antibodies, Bifunctional,Antibodies, Bispecific Monoclonal,Monoclonal Antibodies, Bispecific

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