Impact of charge patches on tumor disposition and biodistribution of therapeutic antibodies

被引：0
作者：
Jakob C. Stüber
Karin F. Rechberger
Saša M. Miladinović
Thomas Pöschinger
Tamara Zimmermann
Remi Villenave
Miro J. Eigenmann
Thomas E. Kraft
Dhaval K. Shah
Hubert Kettenberger
Wolfgang F. Richter
机构：
[1] Roche Diagnostics GmbH,Roche Pharma Research and Early Development, Roche Innovation Center Munich
[2] Present address: Formycon AG,Roche Pharma Research and Early Development, Roche Innovation Center Basel
[3] F. Hoffmann-La Roche Ltd.,Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences
[4] The State University of New York at Buffalo,undefined
来源：
AAPS Open | / 8卷 / 1期
关键词：
Monoclonal antibodies; Biodistribution; Charge dependence;
D O I：
10.1186/s41120-021-00048-9
中图分类号：
学科分类号：
摘要：
This study explores the impact of antibody surface charge on tissue distribution into various tissues including tumor. Tumor-bearing mice were dosed intravenously with a mixture comprising three antibodies engineered to carry negative charge patches, a balanced charge distribution, or positive patches, respectively (cassette dosing). Tissue levels were analyzed with a specific LC-MS/MS method. In addition, the antibody mix was administered to non-tumor bearing mice. Muscle and skin interstitial fluid were obtained by centrifugation and analyzed by LC-MS/MS. An in vitro endothelium model was explored for its feasibility to mimic the observed distribution differences.
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