OBINUTUZUMAB Humanized Anti-CD20 Monoclonal Antibody Apoptosis Inducer Oncolytic

The emergence of anti-CD20 monoclonal antibodies (MAbs), especially rituximab, has dramatically improved the treatment of B-cell malignancies during the past 10 years. However, many patients still experience refractory forms and short-term relapses. Obinutuzumab (CA 101; formerly afutuzumab) is the first humanized and glycoengineered type II anti-CD20 MAb to enter clinical development. As illustrated in recent biological studies, obinutuzumab exhibits much stronger activity than rituximab against non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) cells. Despite inferior complement-dependent cytotoxicity, it demonstrates enhanced direct cell death and antibody-dependent cellular cytotoxicity mechanisms, suggesting the possibility to overcome resistance to rituximab. The first early clinical trials of obinutuzumab in relapsed/refractory indolent and aggressive NHL and in CLL patients showed significant overall response rates and a good tolerability profile. Phase Ill trials are currently being conducted to assess the role of obinutuzumab in combination with conventional therapy in B-cell malignancies.