These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Enhanced endocytosis in cultured human breast carcinoma cells and in vivo biodistribution in rats of a humanized monoclonal antibody after cationization of the protein.
    Author: Pardridge WM, Buciak J, Yang J, Wu D.
    Journal: J Pharmacol Exp Ther; 1998 Jul; 286(1):548-54. PubMed ID: 9655901.
    Abstract:
    For monoclonal antibody therapeutics to access target antigen in extravascular compartments, an antibody drug delivery technology is required that has the dual properties of 1) transendothelial migration of the antibody and 2) endocytosis of the antibody into the target cell. These two objectives may be achieved with antibody cationization, and the present studies examine the feasibility of cationizing the humanized 4D5 monoclonal antibody directed against the p185HER2 oncogenic protein. The cationized antibody binds to the p185HER2 extracellular domain with an ED50 of 35 micrograms/ml and inhibits SK-BR3 cell proliferation similar to the native antibody. Confocal microscopy showed that although there was binding of the native 4D5 antibody to the plasma membrane of SK-BR3 cells, this antibody was confined to the periplasma membrane space with minimal endocytosis into the cell. In contrast, robust internalization of the cationized 4D5 antibody by the SK-BR3 cells was demonstrated by confocal microscopy. The systemic volume of distribution of the cationized 4D5 antibody was 11-fold greater than that of the native antibody. In summary, these studies show that a humanized monoclonal antibody may be cationized with retention of antibody affinity for the target antigen and biological activity, yet with a marked alteration in the cellular distribution and pharmacokinetics in vivo.
    [Abstract] [Full Text] [Related] [New Search]