TY - JOUR
T1 - Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor
AU - Jaggi, Jaspreet Singh
AU - Carrasquillo, Jorge A.
AU - Seshan, Surya V.
AU - Zanzonico, Pat
AU - Henke, Erik
AU - Nagel, Andrew
AU - Schwartz, Jazmin
AU - Beattie, Brad
AU - Kappel, Barry J.
AU - Chattopadhyay, Debjit
AU - Xiao, Jing
AU - Sgouros, George
AU - Larson, Steven M.
AU - Scheinberg, David A.
PY - 2007/9/4
Y1 - 2007/9/4
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI32226
DO - 10.1172/JCI32226
M3 - Article
C2 - 17717602
AN - SCOPUS:34848838291
SN - 0021-9738
VL - 117
SP - 2422
EP - 2430
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 9
ER -