Milatuzumab immunoliposomes induce cell death in CLL by promoting accumulation of CD74 on the surface of B cells.
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.
Hertlein
Erin
E
Department of Internal Medicine, Division of Hematology, the Comprehensive Cancer Center at The Ohio State University, Columbus, OH 43210, USA.
Triantafillou
Georgia
G
Sass
Ellen J
EJ
Hessler
Joshua D
JD
Zhang
Xiaoli
X
Jarjoura
David
D
Lucas
David M
DM
Muthusamy
Natarajan
N
Goldenberg
David M
DM
Lee
Robert J
RJ
Byrd
John C
JC
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
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