Since the first description of monoclonal antibodies (mAbs) by Kohler and Milstein in 1975,1
numerous advances in molecular biology and biotechnology have streamlined the identification, genetic manipulation, and recombinant production of such antibodies. Over the past decade the use of antibodies has spread into different fields in medicine, such as autoimmune diseases, hematological disorders, cardiovascular diseases, infectious diseases, and diagnostics.2
Also, in the treatment of solid human tumors, biological therapeutics have emerged and gained importance for a growing number of cancer entities.
In the treatment of solid human tumors, biological therapeutics have also emerged and gained importance for a growing number of cancer forms. In contrast to conventional therapeutics such as chemotherapeutics or radiation, which both impose a high burden on nontumor tissue, the use of biological therapeutics aims at more specific, targeted therapy.
The concept of targeted therapy was facilitated by greater understanding of the biological pathways involved in the pathogenesis of cancer, and subsequently identification of cell surface antigens and bioactive molecules.5
A rather specific, and thus restrictive, expression pattern of these antigens and molecules in human tissue enables locally-focused targeting of antibodies to tumor tissue itself, as well as to nonneoplastic cells and substances relevant for tumor biology.
The introduction of mAbs in tumor therapy had a significant impact on pathological processes, particularly malignancies of solid and hematological origin. In particular, the use of mAbs has been established as mono, combination, first- and second-line, as well as palliative therapies. Their selectivity and specificity, unique pharmacokinetics, and ability to engage and activate the immune system differentiate these biologics from other small molecule anticancer drugs.
This review summarizes the currently established biological therapeutics for treating solid tumors, with emphasis on the mAbs that have been approved by the United States Food and Drug Administration (FDA) for clinical use, as well as ongoing phase III studies and current Fc fusion proteins as of June 2011. Furthermore, the focus is on the targeted proteins and observed treatment effects associated with each antibody, the registration trials for their approved indications, and new emerging indications.