OBJECTIVE: The objective of this study was to determine the properties of a single-chain bispecific antibody (scBsAb) against human ovarian carcinoma and to develop this agent for potential use in human ovarian cancer. METHODS: ELISA and FACS were performed to determine the antigen-binding properties of the scBsAb. Its abilities to retarget the pre-activated human peripheral blood mononuclear cells (PBMCs) to human ovarian carcinoma cell line SKOV3 cells and mediate their lysis in vitro were performed by a colorimetric MTT-based assay. Nude mice bearing human SKOV3 tumor xenografts were used to study the distribution and imaging of the scBsAb. Its pharmacokinetics in vivo was also studied in naive BALB/c mice. RESULTS: The scBsAb showed nearly identical ligand binding properties at each site relative to the individual monovalent single-chain antibody prototype molecules and could bridge SKOV3 and human T cell line Jurkat, which expresses CD3 antigens on the surface of cells together. It can also retarget the pre-activated PBMCs to SKOV3 cells and mediated their lysis in vitro effectively. Imaging and distribution study demonstrated that the antibody could target the tumor. Its elimination in vivo corresponded to second-order kinetics with a terminal half-life time (t(1/2)beta) of 7.7 h. CONCLUSION: This scBsAb with easy production and reasonable blood retention time should be developed for potential use in human ovarian cancer.
OBJECTIVE: The objective of this study was to determine the properties of a single-chain bispecific antibody (scBsAb) against humanovarian carcinoma and to develop this agent for potential use in humanovarian cancer. METHODS: ELISA and FACS were performed to determine the antigen-binding properties of the scBsAb. Its abilities to retarget the pre-activated human peripheral blood mononuclear cells (PBMCs) to humanovarian carcinoma cell line SKOV3 cells and mediate their lysis in vitro were performed by a colorimetric MTT-based assay. Nude mice bearing human SKOV3 tumor xenografts were used to study the distribution and imaging of the scBsAb. Its pharmacokinetics in vivo was also studied in naive BALB/c mice. RESULTS: The scBsAb showed nearly identical ligand binding properties at each site relative to the individual monovalent single-chain antibody prototype molecules and could bridge SKOV3 and human T cell line Jurkat, which expresses CD3 antigens on the surface of cells together. It can also retarget the pre-activated PBMCs to SKOV3 cells and mediated their lysis in vitro effectively. Imaging and distribution study demonstrated that the antibody could target the tumor. Its elimination in vivo corresponded to second-order kinetics with a terminal half-life time (t(1/2)beta) of 7.7 h. CONCLUSION: This scBsAb with easy production and reasonable blood retention time should be developed for potential use in humanovarian cancer.