Small antibody mimetics comprising two complementarity-determining regions and a framework region for tumor targeting
| Autor: | Xiao-Qing Qiu, Shi-Tao Yue, Bei Cai, He Wang, Lan-Lan Wang |
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| Rok vydání: | 2007 |
| Předmět: |
Biomedical Engineering
Bioengineering Complementarity determining region Applied Microbiology and Biotechnology Drug Delivery Systems Antigen Biomimetics Neoplasms Animals Humans Cytotoxic T cell Binding site Framework region Genetics biology Antibodies Monoclonal Fusion protein Protein Structure Tertiary Cell biology Molecular Weight Drug Design Colicin biology.protein Molecular Medicine Antibody Biotechnology |
| Zdroj: | Nature Biotechnology. 25:921-929 |
| ISSN: | 1546-1696 1087-0156 |
| Popis: | Here we show that fusion of two complementarity-determining regions (CDRs), VHCDR1 and VLCDR3, through a cognate framework region (VHFR2) yields mimetics that retain the antigen recognition of their parent molecules, but have a superior capacity to penetrate tumors. The antigen-recognition abilities of these approximately 3 kDa mimetics surpass those of comparable fragments lacking the framework region. In vivo activities of the mimetics suggests that the structural orientation of their CDRs approximates the conformation of the CDRs in the complex of the parent antibody with antigen. We linked the antibody mimetics to the bacterial toxin colicin Ia to create fusion proteins called "pheromonicins," which enable targeted inhibition of tumor growth. In mice bearing human malignant tumors, pheromonicins directed against tumor-specific surface markers show greater capacity to target and penetrate tumors than their parent antibodies. Rational recombination of selected VH/VL binding sites and their framework regions might provide useful targeting moieties for cytotoxic cancer therapies. |
| Databáze: | OpenAIRE |
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