Monoclonal antibody therapy of non-Hodgkin's lymphoma: the Rituximab story.

The advent of monoclonal antibodies targeted at tumor associated or tumor specific antigens provides a novel approach for the treatment of a broad range of malignancies. Such targeting agents can either be used as unlabeled molecules to induced antibody dependent cytotoxicity, or complement mediated lysis and/or apoptosis, or be conjugated with cytotoxic moieties such as toxins and/or radioactive nucleids. The applicability of this strategy has been expanded beyond the treatment of NHL as demonstrated by the clinical application of the chimeric monoclonal antibody directed at the Her2/neu receptor in breast cancer, the epidermal growth factor receptor in colon and head/neck cancer, and the vascular endothelial growth factor in lung and colon cancer, among others. In a variety of settings this strategy demonstrates clinical anti-tumor activity in patients who have failed to respond to or are refractory to conventional cytotoxic chemotherapy. Furthermore, given the modest toxicity of these naked antibodies, they avail themselves as ideal partners for combining with conventional chemotherapy to produce results that often appear to be greater than additive. With the discovery of newer targets and means to manipulate the immunoglobulin molecule to generate tailor made antibody fragments, the field of antibody based targeted therapy of cancer appears to be on the threshold of making major strides in the fight against cancer.