title: Milatuzumab-conjugated liposomes as targeted dexamethasone carriers for therapeutic delivery in CD74+ B-cell malignancies.
abstract: OBJECTIVE
  Corticosteroids are widely used for the treatment of B-cell malignancies, including non-Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), and acute lymphoblastic leukemia; however, this class of drug is associated with undesirable off-target effects. Herein, we developed novel milatuzumab-conjugated liposomes as a targeted dexamethasone carrier for therapeutic delivery in CD74(+) B-cell malignancies and explored its effect against the disease.
  
  
  METHODS
  The targeting efficiency of milatuzumab-targeted liposomes to CD74(+) cells was evaluated in vitro. The effect of CD74-targeted liposomal dexamethasone was compared with free dexamethasone in primary CLL cells and cell lines in vitro. The therapeutic efficacy of CD74-targeted liposomal dexamethasone was evaluated in a Raji-severe combined immunodeficient (SCID) xenograft model in vivo.
  
  
  RESULTS
  Milatuzumab-targeted liposomes promoted selective incorporation of carrier molecules into transformed CD74-positive B cells as compared with CD74-negative T-cells. The CD74-dexamethasone-targeted liposomes (CD74-IL-DEX) promoted and increased killing in CD74-positive tumor cells and primary CLL cells. Furthermore, the targeted drug liposomes showed enhanced therapeutic efficacy against a CD74-positive B-cell model as compared with free, or non-targeted, liposomal dexamethasone in SCID mice engrafted with Raji cells in vivo.
  
  
  CONCLUSIONS
  These studies provide evidence and support for a potential use of CD74-targeted liposomal dexamethasone as a new therapy for B-cell malignancies.
authors.affiliation: Division of Hematology, The Comprehensive Cancer Center, Division of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Mao
authors.forename: Georgia
authors.initials: G
authors.lastname: Triantafillou
authors.forename: Erin
authors.initials: E
authors.lastname: Hertlein
authors.forename: William
authors.initials: W
authors.lastname: Towns
authors.forename: Matthew
authors.initials: M
authors.lastname: Stefanovski
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.forename: David
authors.initials: D
authors.lastname: Jarjoura
authors.forename: Mitch
authors.initials: M
authors.lastname: Phelps
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Ly James
authors.initials: LJ
authors.lastname: Lee
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Natarajan
authors.initials: N
authors.lastname: Muthusamy
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008081:Liposomes; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D051379:Mice; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008081:Liposomes; C045084:invariant chain; C540932:milatuzumab; D003907:Dexamethasone