The Current Status and Issues Concerning Monoclonal Antibody Therapy

Monoclomal antibodies (mAbs) against growth factor or its receptor have raised the second wave of antibody therapy for solid tumors. Transtuzumab (humanized anti-HER2mAb) is the first mAb approved for the treatment of a solid tumor, metastatic breast cancer. Large-scale phase Ⅲ clinical trials are now ongoing to further evaluate the additive effects on chemotherapy and the efficacy as a maintenance monotherapy. Overexpression of HER2 is found only a small percentage of patients with solid tumor, whereas epidermal growth factor receptor is expressed in a variety of solid tumors with high frequency. More broadly applicable for solid tumors is anti-angiogenesis therapy because it is targeting not tumor cells but tumor vasculature. Cetuximab (chimeric anti-EGFR mAb) and bevacizumab (humanized anti-VEGF mAb)have recently been shown to be clinically of remarkable effect for metastatic colorectal cancer. The points at issue are thrombotic events of bevacizumab. In contrast to the mAbs as signal inhibitors, no apparent objective responses were seen in most clinical studies of mAbs against cell surface glycoproteins or adhesion molecules. However, several groups reported the survival benefit of those mAbs, in which anti-idiotypic antibody response may play an important role. In addition, some of their anti-idiotype mAbs showed the survival benefit in patients with solid tumor. Altered self-antigens have recently been attempted to intensify active immunotherapy including dendritic cell therapy. Considering that dendritic cells efficientry cross-present tumor antigens after ingesting them as immune complex those ”modest″ mAbs may be of use for dendritic cell therapy as immune complex with altered self-antigens.

monoclonal antibody

HER2

epidermal growth factor receptor

vascular endothelial growth factor

VEGF receptor

human anti-mouse antibody

epithelial cell adhesion molecule

cytotoxic T lymphocyte-associated antigen 4

dendritic cells