First published November 1, 2007 - More info
The long plasma half-life of IgG, while allowing for enhanced tumor uptake of tumor-targeted IgG conjugates, also results in increased background activity and normal-tissue toxicity. Therefore, successful therapeutic uses of conjugated antibodies have been limited to the highly sensitive and readily accessible hematopoietic tumors. We report a therapeutic strategy to beneficially alter the pharmacokinetics of IgG antibodies via pharmacological inhibition of the neonatal Fc receptor (FcRn) using high-dose IgG therapy. IgG-treated mice displayed enhanced blood and whole-body clearance of radioactivity, resulting in better tumor-to-blood image contrast and protection of normal tissue from radiation. Tumor uptake and the resultant therapeutic response was unaltered. Furthermore, we demonstrated the use of this approach for imaging of tumors in humans and discuss its potential applications in cancer imaging and therapy. The ability to reduce the serum persistence of conjugated IgG antibodies after their infusion can enhance their therapeutic index, resulting in improved therapeutic and diagnostic efficacy.
Jaspreet Singh Jaggi, Jorge A. Carrasquillo, Surya V. Seshan, Pat Zanzonico, Erik Henke, Andrew Nagel, Jazmin Schwartz, Brad Beattie, Barry J. Kappel, Debjit Chattopadhyay, Jing Xiao, George Sgouros, Steven M. Larson, David A. Scheinberg
Original citation: J. Clin. Invest.117:2422-2430 (2007). doi:10.1172/JCI32226.
Citation for this corrigendum: J. Clin. Invest.117:3593 (2007). doi:10.1172/JCI32226C1.
During the preparation of the manuscript, the Ludwig Center for Cancer Immunotherapy was inadvertently omitted from the Acknowledgments. The correct Acknowledgments section appears below.
A33 and cG250 antibodies were a gift from the Ludwig Institute of Cancer Research. We thank Adam Boruchov and Chaitanya Divgi for helpful discussions. We thank the Ludwig Center for Cancer Immunotherapy for support. This work was supported by grants from the NIH (R01CA55349 and P01CA33049), the Doris Duke Foundation, the Ludwig Institute of Cancer Research, the Joseph LeRoy and Ann C. Warner Fund, and the William and Alice Goodwin Commonwealth Foundation.
The authors regret the error.