Action and resistance of monoclonal CD20 antibodies therapy in B-cell Non-Hodgkin Lymphomas

Cancer Treat Rev. 2015 Sep;41(8):680-9. doi: 10.1016/j.ctrv.2015.05.007. Epub 2015 May 19.

Abstract

Anti-CD20 monoclonal antibodies (mAbs) have improved patient's survival with Non-Hodgkin Lymphoma, when combined with chemotherapy. Several mechanisms of action have been reported, including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and induction of apoptosis. Despite the large amount of studies and published data, the role each mechanism played in vivo is not fully understood. Furthermore, the reason why a significant percentage of patients are refractory or resistant remains unknown. Several activated intracellular signaling pathways have been implicated in the mechanisms of resistance of rituximab. In the present manuscript, we review those mechanisms and new anti-CD20 mAbs, as well as the efforts being accomplished to overcome it, focusing on new drugs targeting pathways implicated in resistance to rituximab.

Keywords: Apoptosis; CD20; Monoclonal antibodies; Non-Hodgkin Lymphomas; Rituximab.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Antibody-Dependent Cell Cytotoxicity / drug effects*
  • Antigens, CD20 / immunology*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Drug Resistance, Neoplasm*
  • Drug Therapy / methods
  • Drug Therapy / trends
  • Humans
  • Lymphoma, B-Cell* / drug therapy
  • Lymphoma, B-Cell* / immunology
  • Rituximab
  • Therapies, Investigational

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Antineoplastic Agents
  • Rituximab