2D7 diabody bound to the alpha2 domain of HLA class I efficiently induces caspase-independent cell death against malignant and activated lymphoid cells.
A mouse monoclonal antibody (2D7 mAb), which specifically bound to the alpha2 domain of HLA class I, rapidly induces cell aggregation accompanied by weak cytotoxicity against ARH-77 cells, suggesting that 2D7 mAb had a potential for agonist antibody. In order to enhance this cytotoxicity, 2D7 mAb was engineered to be a small bivalent antibody fragment, 2D7 diabody. The resultant 2D7 diabody showed a strong cytotoxicity against ARH-77 cells. As a notable characteristic feature, the lethal effect of 2D7 diabody was quite rapid, mediated by a caspase-independent death pathway. Furthermore, 2D7 diabody also showed cytotoxicity against several leukemia and lymphoma cell lines, and mitogen-activated peripheral blood mononuclear cells (PBMC), but not for normal resting PBMC and adherent cell lines such as HUVEC. These results suggest that 2D7 diabody could be expected as a novel therapeutic antibody for hematological malignancies as well as inflammatory diseases.
Kimura
Naoki
N
Genome Antibody Product Research Department, Chugai Pharmaceutical Co., Ltd., Japan. kimuranok@chugai-pharm.co.jp
Kawai
Shigeto
S
Kinoshita
Yasuko
Y
Ishiguro
Takahiro
T
Azuma
Yumiko
Y
Ozaki
Shuji
S
Abe
Masahiro
M
Sugimoto
Masamichi
M
Hirata
Yuichi
Y
Orita
Tetsuro
T
Okabe
Hisafumi
H
Matsumoto
Toshio
T
Tsuchiya
Masayuki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D016466:CHO Cells; D020169:Caspases / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D020169:Caspases