Over the past two decades, monoclonal antibodies have emerged as a versatile class of therapeutics with unique properties. More than 30 therapeutic antibodies are now approved in the United States and European Union, with numerous candidates filling the preclinical and clinical pipeline of every major pharmaceutical companies and biotechnology firms. Monoclonal antibodies have the advantage over traditional medicines in that they are able to specifically bind to the desired targets with little to no associated toxicity. In the recent years, monoclonal antibodies approved for oncology treatments have gained in notoriety and are now used as adjuvants or neo-adjuvants to radiotherapy, chemotherapy and surgery. In the field of head and neck cancer, the anti-EGF receptor antibody Erbitux has paved the way for new targeted treatments to SCCHN. This review introduces some basic concepts and recent perspectives on monoclonal antibodies with a focus on head and neck cancer treatments.
Immunobiology: The immune system in health and disease (5th ed). Garland Science: New York 2001.
Immunoglobulin structure and function as revealed by electron microscopy. Int Arch Allergy Immunol 1999;120: 85-99.
Fc receptors and their interactions with immunoglobulins. Annual Review of Cell and Developmental Biology 1996;12:181-220.
Structural basis of antibody function. Annual Review of Immunology 1983;1:87-115.
Structure and function of the B-cell antigen receptor. Annual Review of Cell Biology 1993;9:377-410.
Human antibody-Fc receptor interactions illuminated by crystal structures. Nat Rev Immunol 2004;4: 89-99.
In annual review of immunology 199816545-6. (annual reviews).
Complement ligand-receptor interactions that mediate biological responses. Annual Review of Immunology 1983;1:243-71.
Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev 2005;24:487-99.
Neonatal Fc receptor mediates internalization of Fc in transfected human endothelial cells. Mol Biol Cell 2008;19:5490-5505.
Hybrid hybridomas and their use in immunohistochemistry. Nature 1983;305:537-40.
Three decades of human monoclonal antibodies: Past, present and future developments. Hum Antibodies 2009;18:1-10.
Fully human antibodies from transgenic mouse and phage display platforms. Curr Opin Immunol 2008;20:450-59.
Human monoclonal antibodies from transgenic mice. Handb Exp Pharmacol 2008;69-97.
Artificial, non-antibody binding proteins for pharmaceutical and industrial applications. Trends Biotechnol 2005;23:514-22.
Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov 2009;8:226-34.
Optimizing engagement of the immune system by anti-tumor antibodies: An engineer's perspective. Drug Discov Today 2007;12: 898-910.
Antibody-drug conjugates for cancer therapy. Cancer J 2008;14:154-69.
A revival of bispecific antibodies. Trends Biotechnol 2004;22:238-44.
Catumaxomab: Clinical development and future directions. MAbs 2.
Drug delivery to the posterior segment of the eye. Drug Discov Today 16:270-77.
Efficient intraocular penetration of topical anti-TNF-? single-chain antibody (ESBA105) to anterior and posterior segment without penetration enhancer. Investigative Ophthalmology and Visual Science 2009;50:779-86.
Pulmonary administration of therapeutic proteins using an immunoglobulin transport pathway. Adv Drug Deliv Rev 2006;8:1106-18.
Targeting epidermal growth factor receptor in head and neck cancer: Lessons learned from cetuximab. Exp Biol Med (Maywood) 235:907-20.
Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum-based therapies. Cancer 2008;112:2710-19.
Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008; 359:1116-27.
Panitumumab: Human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. Clin Ther 2008;30: 14-30.
Cetuximab and panitumumab: Are they interchangeable? Lancet Oncol 2009;10:1140-41.
8519 A phase 2, randomized trial (CONCERT-1) of chemoradiotherapy with or without panitumumab in patients (pts) with unresected, locally advanced squamous cell carcinoma of the head and neck (SCCHN): Interim pooled safety analysis. European Journal of Cancer Supplements 2009;7: 476-76.
8516 A phase 2 randomized trial of radiotherapy (RT) plus panitumumab compared to chemoradiotherapy in patients with unresected, locally advanced squamous cell carcinoma of the head and neck (SCCHN): Interim pooled safety analysis. European Journal of Cancer Supplements 2009;7: 475-75.
8514 Spectrum, a phase III trial for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) receiving chemotherapy with or without panitumumab: Interim pooled safety analysis. European Journal of Cancer Supplements 2009;7:474-75.
The antibody zalutumumab inhibits epidermal growth factor receptor signaling by limiting intra- and intermolecular flexibility. Proc Natl Acad Sci USA 2008;105:6109-114.
Dual mode of action of a human antiepidermal growth factor receptor monoclonal antibody for cancer therapy. The Journal of Immunology 2004;173:4699-707.
Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: An open-label, randomised phase 3 trial. The Lancet Oncology 12:333-43.
Nimotuzumab: A novel anti-EGFR monoclonal antibody that retains anti-EGFR activity while minimizing skin toxicity. Expert Opin Biol Ther 2009;9: 1199-1206.
Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor. J Clin Oncol 2004;22:175-84.
Phase I study of epirubicin, cisplatin and capecita- bine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer. Br J Cancer 2008;99: 868-74.
Cetuximab and other anti-epidermal growth factor receptor monoclonal antibodies in the treatment of non-small cell lung cancer. Oncologist 2009; 14:601-11.
Targeting the future in head and neck cancer. Lancet Oncol 2009;10:204-05.
Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: A phase I/II study. Lancet Oncol 2009;10:247-57.
Should we be surprised at the paucity of response to EGFR inhibitors? Lancet Oncol 2009;10: 522-27.