Pharmacokinetics and Biodistribution Study of 7A7 Anti-Mouse Epidermal Growth Factor Receptor Monoclonal Antibody and Its Fragment in an Immunocompetent Mouse ModelReport as inadecuate




Pharmacokinetics and Biodistribution Study of 7A7 Anti-Mouse Epidermal Growth Factor Receptor Monoclonal Antibody and Its Fragment in an Immunocompetent Mouse Model - Download this document for free, or read online. Document in PDF available to download.

ISRN PharmacologyVolume 2012 2012, Article ID 417515, 8 pages

Research Article

Tumor Immunology Direction, Molecular Immunology Institute, Center of Molecular Immunology, 216 Street, 15th Avenue, Atabey, Siboney, Playa, P.O. Box 16040, 11600 Havana, Cuba

Departments of Pharmacology and Toxicology, Institute of Pharmacy and Foods, University of Havana, 11600 Havana, Cuba

Radiobiology Laboratory, Center for Radiation Protection and Hygiene, 11600 Havana, Cuba

Received 8 October 2012; Accepted 23 October 2012

Academic Editors: K. Cimanga, G. Gervasini, T. Kumai, and T. B. Vree

Copyright © 2012 Ailem Rabasa Capote et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Immunocompetent mice, Fc receptor γ-chain deficient mice , and molecular tools as Fab′2 bivalent fragments appear as the most suitable biological models to study the mechanisms of the action of anti-epidermal growth factor receptor EGFR monoclonal antibodies mAbs. In vivo experiments contrasting antitumor effects of whole Abs and their bivalent fragments commonly involve a previous comparative pharmacokinetics study. In this paper, pharmacokinetics and biodistribution of an anti-mouse EGFR Ab were assessed using immunocompetent mice.

I-labeled 7A7 mAb holds an elimination half-life of 23.1 h in C57BL-6 mice. Accumulation of mAb was found in liver, spleen, kidneys, and mostly in lungs. We used an ELISA method to determine the of a 7A7 mAb using the same experimental setting. Results from this new analysis revealed a of 23.9 h, supporting this method as a safer and easier system to evaluate pharmacokinetics parameters of mAbs targeting mouse EGFR. Using this system we also studied pharmacokinetics of 7A7 Fab′2 fragment. A tenfold difference between the mAb and fragment was found. These data support the use of the 7A7 Fab′2 fragment in in vivo studies to explore the contribution of the EGFR signaling blockade and the Fc region to the antitumor effect of 7A7 mAb in this autologous scenario.





Author: Ailem Rabasa Capote, Jorge Ernesto González, Leyanis Rodríguez-Vera, Armando López, Belinda Sánchez Ramírez, and Greta G

Source: https://www.hindawi.com/



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