The preclinical discovery of rituximab for the treatment of non-Hodgkin’s lymphoma

Abstract

Introduction: Monoclonal antibodies (MoAbs) were developed in the 1980s in order to treat malignancies. An important target for MoAbs was the CD20 B-cell lineage antigen. Rituximab (RTX) is a chimeric mouse anti-human MoAb that targets the CD20 antigen on the surface of malignant and normal B lymphocytes, and has rapidly become the widest used immunotherapeutic drug. RTX has had a significant impact on how B-cell non-Hodgkin’s lymphomas (NHLs) and chronic lymphocytic leukemia is now treated.

Areas covered: In this review, the authors demonstrate the mechanisms of action of RTX, and the preclinical data that have led to clinical trials and its final approval for the treatment of B-cell NHLs.

Expert opinion: The discovery of RTX opened a new era for treatment of B-cell malignancies and became the starting point for the development of new, more active classes of anti-CD20 agents. Furthermore, it has contributed to the construction of a number of MoAbs specific for other antigens that target different types of neoplastic cells.

Keywords:

• antibody-dependent cell-mediated cytotoxicity
• apoptosis
• B-cell malignancies
• complement-dependent cytotoxicity
• direct cell death
• non-Hodgkin’s lymphoma
• rituximab

Declaration of interest

This work was supported in part by a grant from the Medical University of Lodz (No. 503/1-1093-01/503-01) and by the Foundation for the Development of Diagnostics and Therapy, Warsaw, Poland. T Robak has received research grants from Hoffmann-La Roche, GlaxoSmithKline, Trubion Pharmaceuticals Inc, Janssen Pharmaceuticals, Pharmacyclics and Gilead Sciences, as well as travel grants from Hoffmann-La Roche. P Smolewski received research grants from Hoffmann-La Roche and Gilead Sciences, and travel grants from Hoffmann-La Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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