title: A new design immunotoxin for killing high-grade glioma U87 cells: from in vitro to in vivo.
abstract: A new wave of engineered antibodies, leading to increased effectiveness of functions such as antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity, is being evaluated in clinical settings. Several, such as immunotoxins, are expected to receive approval for usage soon. In this study, using a cognate heavy framework region (HFR2), two complementarity-determining regions (CDRs, i.e., LCDR1 and HCDR3) were fused to the first 388 amino acid residues of diphtheria toxin (DT388) to establish the immunotoxin IT-87. It was found that the mimetics of LCDR1-HFR2-HCDR3 retained the antigen recognition of their parent antibody. The immunotoxin IT-87 could especially kill the U87 MG glioblastoma cell line, the targets of the parent antibody, in vitro; however, the IT-87 could not kill Rajicells. In SCID mice bearing both U87 and Raji cells, the IT-87 directly targeted the U87-induced tumors (via tumor-specific surface markers) and inhibited the growth of the cells in vivo over a 20-day daily IT-87 treatment period. It is believed that the design of this particular immunotoxin could be the basis for even more promising molecules to be used in the treatment of human cancers.
authors.affiliation: Guangdong Institute of Neurosurgery, Guangdong Province Key Laboratory of Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, PR China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Luqiu
authors.forename: Ke
authors.initials: K
authors.lastname: Yiquan
authors.forename: Ling
authors.initials: L
authors.lastname: Gengqiang
authors.forename: Liu
authors.initials: L
authors.lastname: Yijing
authors.forename: Jiang
authors.initials: J
authors.lastname: Xiaodan
authors.forename: Cai
authors.initials: C
authors.lastname: Yingqian
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics; D000951:Antigens, Neoplasm / Q000276:immunology; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D022801:Complementarity Determining Regions / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000235:genetics; D015195:Drug Design; D000939:Epitopes; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D010446:Peptide Fragments / Q000235:genetics; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D022801:Complementarity Determining Regions; D004167:Diphtheria Toxin; D000939:Epitopes; C581145:IT-87 immunotoxin; D000922:Immunotoxins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins