Milatuzumab immunoliposomes induce cell death in CLL by promoting accumulation of CD74 on the surface of B cells

• Published in: Blood 2010-10, Vol.116 (14), p.2554-2558
• Main Authors: Hertlein, Erin, Triantafillou, Georgia, Sass, Ellen J., Hessler, Joshua D., Zhang, Xiaoli, Jarjoura, David, Lucas, David M., Muthusamy, Natarajan, Goldenberg, David M., Lee, Robert J., Byrd, John C.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antigens, Differentiation, B-Lymphocyte - immunology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - immunology; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Blood; Cell death; Cell Death - drug effects; Cell surface; Chronic lymphatic leukemia; Cytotoxicity; Data processing; Hematologic and hematopoietic diseases; Histocompatibility Antigens Class II - immunology; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Liposomes; Lymphocytes B; Lymphoid Neoplasia; Medical sciences; Monoclonal antibodies; Translation
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2009-11-253203

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.