title: Milatuzumab immunoliposomes induce cell death in CLL by promoting accumulation of CD74 on the surface of B cells.
abstract: Chronic lymphocytic leukemia (CLL) is an incurable progressive disease for which new therapies are required. Therapy with monoclonal antibodies (mAbs) has improved the outcome of patients with CLL, making further investigation of novel antibodies directed against alternative and specific targets on B cells an important area of translational research. We now describe functional properties of an antagonistic humanized mAb to CD74, milatuzumab, showing that milatuzumab combined with a crosslinking antibody induces cytotoxicity in vitro in CLL cells in a caspase- and stromal-independent manner associated with aggregation of CD74 on the cell surface. Furthermore, incorporation of milatuzumab into an immunoliposome induces even more of a cytotoxic response than in vitro crosslinking, representing a novel therapeutic formulation for this mAb. Based on these data, future development of the milatuzumab-immunoliposome formulation as a therapeutic agent for CLL is warranted.
authors.affiliation: Department of Internal Medicine, Division of Hematology, the Comprehensive Cancer Center at The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Hertlein
authors.forename: Georgia
authors.initials: G
authors.lastname: Triantafillou
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Sass
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Hessler
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Jarjoura
authors.forename: David M
authors.initials: DM
authors.lastname: Lucas
authors.forename: Natarajan
authors.initials: N
authors.lastname: Muthusamy
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
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016923:Cell Death / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008081:Liposomes
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; D000949:Histocompatibility Antigens Class II; D008081:Liposomes; C045084:invariant chain; C540932:milatuzumab