Research abstract
Article abstract
Nature Biotechnology 25, 921 - 929 (2007)
Published online: 5 August 2007 | doi:10.1038/nbt1320
Small antibody mimetics comprising two complementarity-determining regions and a framework region for tumor targeting
Xiao-Qing Qiu1, He Wang3, Bei Cai2, Lan-Lan Wang2 & Shi-Tao Yue1
Abstract
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 
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.
- Key Laboratory of Transplant Immunology, Ministry of Health, State Key Laboratory of Biotherapy, No. 37 Wai Nan Guo-xue-Xiang, Chengdu, P.R. of China 610041.
- Department of Lab Medicine, Division of Clinical Immunology, West China Hospital, No. 37 Wai Nan Guo-xue-Xiang, Chengdu, P.R. of China 610041.
- Laboratory of Genetics, West China Second University Hospital, West China School of Medicine, Sichuan University, No. 37 Wai Nan Guo-xue-Xiang, Chengdu, P.R. of China 610041.
Correspondence to: Xiao-Qing Qiu1 e-mail: xqqiu@tfol.com
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