A mouse/human-chimeric bispecific antibody reactive with human carcinoembryonic antigen-expressing cells and human T-lymphocytes.
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.
First Department of Biochemistry, School of Medicine, Fukuoka University, Japan.
M
M
Kuwahara
M
M
Kuroki
F
F
Arakawa
T
T
Senba
Y
Y
Matsuoka
T
T
Hideshima
Y
Y
Yamashita
H
H
Kanda
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D006801:Humans; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000276:immunology
D018033:Antibodies, Bispecific; D017252:CD3 Complex; D002272:Carcinoembryonic Antigen