The clinical pharmacology of therapeutic monoclonal antibodies in the treatment of malignancy; have the magic bullets arrived?

Abstract

Monoclonal antibodies (Mabs) are proteins in the immunoglobulin family that bind to specific protein epitope targets on cancer and stromal cells, allowing them to be successfully exploited as therapeutic agents. The prototype Mabs were produced from fusion of mouse B lymphocytes and mouse myeloma cells and were entirely murine in sequence. Subsequent advances in technology have allowed for humanized Mabs, which have different pharmacokinetic properties than murine Mabs in humans. Mabs antitumour activity is mediated through direct interaction with specific target molecules, deployment of immune cytotoxic pathways, or through chaperoning cytotoxic agents to tumour. Mabs are typically administered intravenously, are generally well tolerated and can have powerful anticancer activity. Humanized Mabs have a t(1/2) in human sera of 2-3 weeks, which determines the frequency of administration. At present, nine clinically approved Mabs are used in the treatment of human cancer, and many others are in clinical trials. We discuss the pharmacology, clinical indications, and toxicity of the currently available anticancer Mabs in this review.