Antibody-DM1 conjugates as cancer therapeutics.

Abstract

Synthetic derivatives of the microtubule-targeted agent maytansine, commonly known as drug maytansinoids or DMs, are emerging as potential cancer therapeutics. DM1 is an antibody-conjugatable maytansinoid that was developed to overcome systemic toxicity associated with maytansine and to enhance tumor-specific delivery. Antibody-DM1 conjugates showed promising results in preclinical and clinical evaluations. However, the molecular mechanism of the drug component DM1 was largely unknown. Recently, researchers have examined the mechanism of DM1 at molecular and cellular levels. According to their findings, DM1 binds at the tips of microtubules and suppresses the dynamicity of microtubules. The antibody-DM1 conjugate cleaves inside cells and releases the active drug in a time-dependent manner. The suppression of microtubule dynamics by DM1 induces mitotic arrest and cell death.

• Authors: Manu Lopus
• Journal: Cancer letters (Cancer Lett) Vol. 307 Issue 2 Pg. 113-8 (Aug 28 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21481526 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antibodies
• Antineoplastic Agents
• Immunoconjugates
• Maytansine

Topics

• Antibodies (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Cell Line, Tumor
• Humans
• Immunoconjugates (therapeutic use)
• Maytansine (analogs & derivatives, therapeutic use)
• Microtubules (drug effects)
• Neoplasms (drug therapy)