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.
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Authors | Zhou Luqiu, Ke Yiquan, Ling Gengqiang, Liu Yijing, Jiang Xiaodan, Cai Yingqian |
Journal | Journal of immunotoxicology
(J Immunotoxicol)
2012 Oct-Dec
Vol. 9
Issue 4
Pg. 353-8
ISSN: 1547-6901 [Electronic] England |
PMID | 22458328
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Monoclonal
- Antigens, Neoplasm
- Complementarity Determining Regions
- Diphtheria Toxin
- Epitopes
- IT-87 immunotoxin
- Immunotoxins
- Peptide Fragments
- Recombinant Fusion Proteins
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Topics |
- Animals
- Antibodies, Monoclonal
(genetics)
- Antigens, Neoplasm
(immunology)
- Brain Neoplasms
(drug therapy)
- Cell Line, Tumor
- Complementarity Determining Regions
(genetics)
- Cytotoxicity, Immunologic
- Diphtheria Toxin
(administration & dosage, genetics)
- Drug Design
- Epitopes
- Glioma
(drug therapy)
- Humans
- Immunotoxins
(administration & dosage, genetics)
- Mice
- Mice, SCID
- Peptide Fragments
(genetics)
- Protein Engineering
- Recombinant Fusion Proteins
(administration & dosage, genetics)
- Xenograft Model Antitumor Assays
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