[Biologic properties of an anti-human ovarian carcinoma/anti-human CD3 single chain bispecific antibody].
OBJECTIVE
Previous routine therapies can' t improve the survival rate of ovarian carcinoma patients. Experimental and pre-clinical data showed that bispecific antibodies could efficiently induce antitumor effect of cytotoxic cells. This study was to investigate the biologic properties of an anti-human ovarian carcinoma/anti-human CD3 single chain bispecific antibody (BHL-I) in vitro, and provide reference for pre-clinical experiment and its application.


METHODS
Peripheral blood lymphocytes (PBLs), isolated from peripheral blood of healthy donors, were treated with BHL-I. The conjugation between PBLs and target ovarian carcinoma SKOV3 cells was observed under reverse microscope; the proliferation of peripheral blood mononuclear cells (PBMCs) and cytotoxicity of PBLs to SKOV3 cells were detected by MTT assay; the concentrations of human interferon-gamma (hIFN-gamma) and human tumor necrosis factor-alpha (hTNF-alpha), secreted by PBLs in the process of killing target cells, were detected by ELISA.


RESULTS
The rosette (PBL-SKOV3) formation rate was significantly higher in BHL-I group than in control group (15.7% vs. 11.1%, P<0.01). BHL-I significantly enhanced the proliferation of PBLs and cytotoxicity of PBLs to SKOV3 cells in the presence of relative antigen (P<0.01); the cytotoxic rate was positively correlated with the rosette formation rate (r=0.946); the concentrations of hIFN-gamma and hTNF-alpha were significantly increased (P<0.01).


CONCLUSIONS
BHL-I could mediate conjugation between PBLs and SKOV3 cells, and activate the cytotoxicity of PBLs which may relate with up-regulation of hIFN-gamma and hTNF-alpha.
Yang
Jie-Zuan
JZ
Institute of Molecular Immunology, Southern Medical University, Guangzhou, Guangdong, 510515, PR China.
Zhang
Zhong
Z
Ma
Li
L
Yao
Xin-Sheng
XS
Zhou
Ming-Qian
MQ
Wang
Xiang-Bin
XB
Wang
Xiao-Ning
XN
D018033:Antibodies, Bispecific / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018033:Antibodies, Bispecific; D017252:CD3 Complex; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma