Veltuzumab (humanized anti-CD20 monoclonal antibody): characterization, current clinical results, and future prospects

Abstract

Veltuzumab is a humanized, anti-CD20 monoclonal IgG₁ antibody (MAb), constructed recombinantly on the framework regions of epratuzumab, with complementarity-determining regions (CDRs) identical to rituximab, except for a single amino acid in CDR3 of the variable heavy chain. Veltuzumab showed anti-proliferative, apoptotic, and antibody-dependent cellular cytotoxicity effects in vitro similar to rituximab, but with significantly slower off-rates and increased complement-dependent cytotoxicity in several human lymphoma cell lines. In addition, very low doses of veltuzumab, given either intravenously or subcutaneously, depleted B cells in normal cynomolgus monkeys, and controlled tumor growth in mice bearing human lymphomas. Clinically, veltuzumab has been studied in > 150 patients with lymphomas and autoimmune diseases. In non-Hodgkin lymphoma (NHL), infusions of 80–750 mg/m² were well tolerated when given once-weekly for four doses, with the only toxicity being transient mild–moderate infusion reactions. Objective tumor responses, including durable complete responses, occurred at all dose levels. Subcutaneous injections of low doses (80–320 mg) have also proved to be safe and pharmacologically active, producing objective responses, including durable complete responses, at rates comparable to those reported with rituximab, in patients with NHL and immune thrombocytopenia.

Keywords:

• CD20
• non-Hodgkin lymphoma
• rituximab
• veltuzumab
• therapy

Acknowledgements

We thank our clinical collaborators and the patients participating in the many trials summarized in this review article, and Henry Founds, PhD, Chien-Hising Chang, PhD, and Edmund A. Rossi, PhD, for collaborating on various preclinical studies discussed herein.

Declaration of Interest: The research of one of the authors (D.M.G.) has been supported in part by National Institutes of Health (NIH) grant PO1-CA103985 from the National Cancer Institute. Two of the authors (D.M.G. and W.A.W.) have employment and senior management positions at Immunomedics, Inc., as well as stock and stock options.