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.