[Specific targeting cytotoxicity to resistant leukemia cells mediated by anti-Pgp/anti-CD3 diabody].
OBJECTIVE
To study the specific targeting cytotoxicity to drug-resistant leukemia cells mediated by anti-Pgp/anti-CD3 diabody.


METHODS
The diabody was purified by affinity chromatography and identified by SDS-PAGE and FACS. The effect of the anti-Pgp/anti-CD3 diabody mediated lysis of Pgp-expressing tumor cells was assayed by human leukemia nude mice xenograft model in vivo.


RESULTS
The diabody was produced in E.coli in a soluble functional form and could bind both Jurkat cells (CD3(+)) and K562/A02 cells (Pgp(+)). The binding rates were 86.25% and 86.26%, respectively. It could inhibit tumor growth by 98.57% and prolonged the survival of mice bearing xenografted K562/A02 cells.


CONCLUSIONS
The diabody was proved to be a potent agent for mediating T lymphocyte cytotoxicity to lyse Pgp expressing tumor cells in vitro and in vivo.
Gao
Ying-dai
YD
State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS & PUMC, Tianjin 300020, China.
Xiong
Dong-sheng
DS
Yang
Ming
M
Xu
Yuan-fu
YF
Shao
Xiao-feng
XF
Peng
Hui
H
Fan
Dong-mei
DM
Yang
Chun-zheng
CZ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000276:immunology; D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018033:Antibodies, Bispecific; D017252:CD3 Complex