Clinical application of obinutuzumab for treating chronic lymphocytic leukemia

Abstract

Alkylators and nucleoside analogs were the main drugs for treatingchronic lymphoblastic leukemia (CLL), which have been replaced by monoclonal antibodies, such as rituximab in the past 10 years for refractory or relapsed CLL. The first-line immunochemotherapy regimen, rituximab combined with nucleoside analogs, significantly increased CLL patients’ first-reaction rate and improved progression-free survival. Despite the long-lasting remissions by the use of chemoimmunotherapy, most CLL patients will relapse eventually. The obinutuzumab (GA101), an updated CD20 antibody, that is thought to achieve a more durable response with unique molecular and functional characteristics. Obinutuzumab is a humanized, monoclonal type II CD20 antibody modified by glycoengineering. The glycoengineered Fc portion enhances the binding affinity to the FcγRIII receptor on immune effector cells, resulting in increased antibody-dependent cellular cytotoxicity and phagocytosis. In addition, the type II antibody binding characteristics of obinutuzumab to CD20 lead to an efficient induction of direct non-apoptotic cell death. This review summarizes the results of clinical studies using obinutuzumab and looks forward to its further application in treating CLL clinically.

Keywords:

• CD20 antibody
• GA101
• obinutuzumab
• chronic lymphocytic leukemia

Acknowledgments

This work was supported by the Standardized Treatment of Recurrent and Refractory Leukemia in Jiangsu Province (number: BL2014078), the Key Medical Projects of Jiangsu Province (ZDXKB2016020), the Foundation for Basic Scientific Research of Southeast University (3290008413).

Disclosure

The authors report no conflicts of interest in this work.