Novel Immunotherapeutic Approaches for Lymphomas

The year 2007 marks the 10th anniversary of approval by the U.S. Food and Drug Adminstration of the first monoclonal antibody for the treatment of cancer. Rituximab, an anti-CD20 chimeric monoclonal antibody, was approved for the treatment of patients with relapsed/refractory low-grade B-cell non-Hodgkin lymphomas. From an immunologic perspective, this therapeutic indication provided the long-elusive validation of immunotherapy as the fourth modality of treatment for patients with cancer. From a clinical perspective, it was hard to imagine then that this nonchemotherapeutic approach would dramatically impact the management of patients with almost every type of B-cell malignancy and that it would even find a place as a therapeutic option for patients with nonmalignant disorders. Although thousands of patients have been treated worldwide with rituximab, there is still debate regarding its mechanism(s) of action. The demonstration that a number of patients do not benefit with this treatment and that no cures have been achieved with single-agent rituximab prompted several investigators to identify those barriers limiting the efficacy of this monoclonal antibody. Here, we summarize what we have learned in the past 10 years about rituximab efficacy and its mechanisms of action and resistance. We also discuss the new generation of monoclonal antibodies, the development of which has been spurred by the widespread success of anti-CD20 MAb therapy.