FTY720-induced blockage of autophagy enhances anticancer efficacy of milatuzumab in mantle cell lymphoma: is FTY720 the next autophagy-blocking agent in lymphoma treatment?

Abstract

Inhibition of the autophagic pathway has recently revealed promising results in increasing pro-death activity of multiple cancer therapeutics. Here, we discuss our findings regarding the autophagy-blocking and anti-neoplastic effects of a synthetic sphingosine analog, FTY720, in mantle cell lymphoma (MCL). We also emphasize how FTY720 enhances the pro-death activity of the fully humanized monoclonal antibody milatuzumab by inhibiting the autophagy-lysosome dependent degradation of its therapeutic target, CD74. Our results provide justification for further evaluation of FTY720 and milatuzumab as a combination therapy for this aggressive B-cell malignancy.

• Authors: Lapo Alinari, Robert A Baiocchi, Mette Praetorius-Ibba
• Journal: Autophagy (Autophagy) Vol. 8 Issue 3 Pg. 416-7 (Mar 2012) ISSN: 1554-8635 [Electronic] United States
• PMID: 22377620 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Neoplasm Proteins
• Propylene Glycols
• milatuzumab
• Fingolimod Hydrochloride
• Sphingosine

Topics

• Animals
• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Autophagy (drug effects)
• Fingolimod Hydrochloride
• Humans
• Lymphoma, Mantle-Cell (drug therapy, pathology)
• Mice
• Neoplasm Proteins (metabolism)
• Phosphorylation (drug effects)
• Propylene Glycols (pharmacology, therapeutic use)
• Sphingosine (analogs & derivatives, pharmacology, therapeutic use)
• Treatment Outcome