Immune response against the murine mdri protein induced by vaccination with synthetic lipopeptides in liposomes

Biochemical and Biophysical Research Communications
Pierre-François TosiC Nicolau

Abstract

Intrinsically, or after exposure to chemotherapeutic drugs, many cancer cells overexpress a class of high molecular weight membrane glycoproteins associated with the multidrug resistance (mdr) of these cells. This report describes an immunization protocol eliciting autoantibodies specific to extracellular epitopes of the murine mdr 1 P-glycoprotein (Pgp). Synthetic peptides with the sequences of extracellular loops of murine Pgp were covalently coupled with four palmitic acid moieties per peptide molecule. These "lipopeptides" were reconstituted in the bilayer of liposomes containing lipid A and used to immunize mice. Antibodies against the lipopeptides corresponding to loop 2 and 4 were elicited in sera of immunized mice. They reacted specifically with extracellular epitopes of the naturally occurring murine Pgp. After interaction with resistant cancer cells, the antibodies induced an average 50% increase in cellular accumulation of doxorubicin and Bodipy-verapamil. In the presence of these antibodies the resistance of L1210 mdr cells was reduced from an LD50 of 4 x 10(-5) M to 5 x 10(-7) M doxorubicin.

Citations

Feb 24, 2011·The Journal of Biological Chemistry·David T HickmanAndreas Muhs
Feb 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Claude NicolauRobert J Hopkins
Feb 14, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·C Pawlak-RoblinC Madoulet
May 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Andreas MuhsClaude Nicolau
Apr 23, 2002·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Enrico CrivellatoGiuliana Decorti

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