title: 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.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, OH, USA.
authors.forename: Lapo
authors.initials: L
authors.lastname: Alinari
authors.forename: Robert A
authors.initials: RA
authors.lastname: Baiocchi
authors.forename: Mette
authors.initials: M
authors.lastname: Praetorius-Ibba
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects*; D000068876:Fingolimod Hydrochloride; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011409:Propylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D011409:Propylene Glycols; C540932:milatuzumab; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine