Doxorubicin-conjugated anti-midkine monoclonal antibody as a potential anti-tumor drug.

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.

• Authors: Kazuhiko Inoh, Hisako Muramatsu, Shuhei Torii, Shinya Ikematsu, Munehiro Oda, Hideshi Kumai, Sadatoshi Sakuma, Tatsuya Inui, Terutoshi Kimura, Takashi Muramatsu
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 36 Issue 4 Pg. 207-11 (Apr 2006) ISSN: 0368-2811 [Print] England
• PMID: 16611663 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Antibodies, Monoclonal
• Cytokines
• Immunotoxins
• Midkine
• Doxorubicin

Topics

• Antibiotics, Antineoplastic (pharmacology, therapeutic use)
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Carcinoma, Hepatocellular (pathology)
• Cell Survival (drug effects)
• Cytokines (immunology)
• Doxorubicin (pharmacology, therapeutic use)
• Humans
• Immunotoxins (pharmacology, therapeutic use)
• Liver Neoplasms (pathology)
• Midkine
• Tumor Cells, Cultured