A Human ICAM-1 Antibody Isolated by a Function-First Approach Has Potent Macrophage-Dependent Antimyeloma Activity In Vivo

作者：Veitonmaki, Niina; Hansson, Markus; Zhan, Fenghuang; Sundberg, Annika; Lofstedt, Tobias; Ljungars, Anne; Li, Zhan-Chun; Martinsson-Niskanen, Titti; Zeng, Ming; Yang, Ye; Danielsson, Lena; Kovacek, Mathilda; Lundqvist, Andrea; Martensson, Linda; Teige, Ingrid; Tricot, Guido; Frendeus, Bjorn^*

来源：Cancer Cell, 2013, 23(4): 502-515.

DOI：10.1016/j.ccr.2013.02.026

• ANTI-CD20 MONOCLONAL-ANTIBODY
• MEDIATED DRUG-RESISTANCE
• C-RECEPTOR POLYMORPHISMS
• MULTIPLE-MYELOMA CELLS
• COMPLEMENT ACTIVATION
• CANCER-CELLS
• ADHESION
• RITUXIMAB
• LYMPHOMA
• THERAPY

We isolated a tumor B-cell-targeting antibody, BI-505, from a highly diversified human phage-antibody library, using a pioneering "function-first" approach involving screening for (1) specificity for a tumor B cell surface receptor, (2) induction of tumor programmed cell death, and (3) enhanced in vivo antitumor activity compared to currently used treatments. BI-505 bound to intercellular adhesion molecule-1, identifying a previously unrecognized role for this receptor as a therapeutic target in cancer. The BI-505 epitope was strongly expressed on the surface of multiple nnyeloma cells from both newly diagnosed and relapsed patients. BI-505 had potent macrophage-dependent antimyeloma activity and conferred enhanced survival compared to currently used treatments in advanced experimental models of multiple nnyeloma.

• 出版日期2013-4-15
• 单位中南大学