Veltuzumab (humanized anti-CD20 monoclonal antibody): characterization, current clinical results, and future prospects.
Veltuzumab is a humanized, anti-CD20 monoclonal IgG(1) 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/m(2) 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.
Goldenberg
David M
DM
Garden State Cancer Center, CMMI, 520 Belleville Ave., Belleville, NJ 07109, USA. dmg.gscancer@att.net
Morschhauser
Franck
F
Wegener
William A
WA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C493846:veltuzumab