Journal article
Tumor targeting by a multivalent single-chain Fv (scFv) anti-Lewis Y antibody construct
MP Kelly, FT Lee, K Tahtis, BE Power, FE Smyth, MW Brechbiel, PJ Hudson, AM Scott
Cancer Biotherapy and Radiopharmaceuticals | MARY ANN LIEBERT, INC | Published : 2008
Abstract
The use of single-chain variable fragment (scFv) constructs has been investigated in cancer radioimmunotherapy (RIT) and radioimmunodetection, as these molecules permit rapid tumor penetration and clearance from the serum relative to whole IgG. Multimerization of scFv constructs has demonstrated improvements in functional affinity (i.e., avidity) and maximal tumor uptake. In this paper, we report the first biodistribution and pharmacokinetics studies of a noncovalent, direct-linked scFv (VL-0-VH) trimeric/tetrameric "multimer" of the anti-Lewis Y monoclonal antibody, hu3S193. The in vitro binding and in vivo biodistribution of the hu3S193 multimer was characterized alongside the hu3S193 F(ab..
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Awarded by National Cancer Institute
Funding Acknowledgements
The authors wish to thank Usha Krishnan for protein purification of the hu3S193 multimer and also Angela Rigopoulos, Dongmao Wang, and Sanja Coso for their assistance in the biodistribution study, Anthony Papenfuss for pharmacokinetic calculations, and the staff from the Department of Nuclear Medicine, Austin Hospital, for their assistance in the gamma-camera imaging of the animals. This research was funded by the NH&MRC Program Grant 290816 and, in part, by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. MPK was supported by a Melbourne Research Scholarship, University of Melbourne (Melbourne, Australia).