Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2422-2430
Number of pages9
JournalJournal of Clinical Investigation
Volume117
Issue number9
DOIs
StatePublished - Sep 4 2007

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor'. Together they form a unique fingerprint.

  • Cite this

    Jaggi, J. S., Carrasquillo, J. A., Seshan, S. V., Zanzonico, P., Henke, E., Nagel, A., Schwartz, J., Beattie, B., Kappel, B. J., Chattopadhyay, D., Xiao, J., Sgouros, G., Larson, S. M., & Scheinberg, D. A. (2007). Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor. Journal of Clinical Investigation, 117(9), 2422-2430. https://doi.org/10.1172/JCI32226