Targeting the CD20 antigen on B lymphocytes with the
monoclonal antibody rituximab has greatly improved
the outcome of patients with B-cell malignancies.
Despite the success of rituximab, resistance occurs in
about half of the patients, resulting in non-response
to treatment or early relapse of the original disease. A
better understanding of the mechanism of rituximab
resistance has lead to the development of novel, improved anti-CD20 antibodies. This review describes the development of CD20-targeted therapy from its historical background towards the next generation of anti-CD20 monoclonal antibodies and explains new strategies to overcome resistance.