RRC ID 42614
Author Inoh K, Muramatsu H, Torii S, Ikematsu S, Oda M, Kumai H, Sakuma S, Inui T, Kimura T, Muramatsu T.
Title Doxorubicin-conjugated anti-midkine monoclonal antibody as a potential anti-tumor drug.
Journal Jpn J Clin Oncol
Abstract BACKGROUND:Midkine is a heparin-binding growth factor preferentially expressed in tumor cells. The present study was performed to utilize anti-midkine antibody for tumor therapy.
METHODS:A monoclonal antibody to midkine was raised by immunizing mice deficient in the midkine gene. The binding site of the antibody was studied by using N-terminal half and C-terminal half of midkine, both of which were chemically synthesized. Doxorubicin (DOX)-conjugate of the antibody was produced by chemical conjugation. The effects of the antibody and the conjugate on cell growth were examined using a midkine-secreting tumor cell, i.e. human hepatocellular carcinoma cell (HepG2).
RESULTS:The monoclonal antibody bound to the N-terminal half of midkine. The antibody did not inhibit the growth of HepG2 cells probably because the active domain of midkine is in the C-terminal half. We produced the antibody conjugated with DOX with the hope that the conjugate would be internalized accompanied with midkine. Indeed, the antibody-DOX conjugate significantly inhibited the growth of HepG2 cells compared with DOX-conjugated control IgG.
CONCLUSION:The result raises the possibility of using anti-midkine antibody conjugated with DOX for cancer therapy.
Volume 36(4)
Pages 207-11
Published 2006-4-1
DOI 10.1093/jjco/hyl004
PII hyl004
PMID 16611663
MeSH Antibiotics, Antineoplastic / pharmacology* Antibiotics, Antineoplastic / therapeutic use Antibodies, Monoclonal / pharmacology Antibodies, Monoclonal / therapeutic use Carcinoma, Hepatocellular / pathology* Cell Survival / drug effects Cytokines / immunology* Doxorubicin / pharmacology* Doxorubicin / therapeutic use Humans Immunotoxins / pharmacology* Immunotoxins / therapeutic use Liver Neoplasms / pathology* Midkine Tumor Cells, Cultured
IF 1.914
Times Cited 19
WOS Category ONCOLOGY
Resource
Human and Animal Cells Hep G2