23.02.2.2. Naked Monoclonal Antibodies

Naked monoclonal antibodies are those that have no cytotoxic chemicals or radionuclides attached to them. They work by either specifically marking the target cell for the immune system to destroy it or attach to cell surface receptors blocking binding of various molecules known to enhance cell growth or proliferation. This group encompasses the vast majority of therapeutic antibodies. Naked monoclonal antibodies have been shown to be particularly effective in the treatment of cancer, autoimmune disease and cardiac disease. An extensive analysis of current use of these antibodies is outwith the remit of this chapter, however, some of the more common treatments are as follows.

Infliximab (Remicade) is a chimeric human-murine monoclonal antibody that binds to human tumour necrosis factor alpha (TNFα). TNFα is a pro-inflammatory and immunoregulatory cytokine that, when overexpressed, mediates chronic inflammation in diseases such as Crohn’s disease and rheumatoid arthritis. Infliximab neutralises the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibits binding of TNFα with its receptors.

Alemtuzumab (MABCampath) is a genetically engineered humanised monoclonal antibody specific for a lymphocyte cell surface glycoprotein, (CD52) antigen. Alemtuzumab causes the lysis of lymphocytes by binding to CD52 antigen, which is expressed on the surface of all B and T lymphocytes (benign and cancerous). As such, alemtuzumab is indicated for the treatment of patients with relapsed B-cell chronic lymphocytic leukaemia (CLL).

Abciximab (ReoPro) is an antibody that binds to the intact platelet GPIIb/IIIa receptor, which is the major platelet surface receptor involved in platelet aggregation. Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. Abciximab is indicated for percutaneous coronary intervention, the prevention of ischaemic cardiac complications in patients undergoing percutaneous coronary intervention (PCI) (balloon angioplasty, atherectomy and stent placement). In patients with unstable angina refractory to conventional treatment, where PCI is planned, it may be used 18 to 24 hours prior to the planned intervention.

Trastuzumab (Herceptin) is a recombinant humanised monoclonal antibody that selectively targets the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2), a protein which is overexpressed in 25%-30% of primary breast cancers. These tumours are particularly aggressive and deliver a shortened disease-free survival compared to patients whose tumours do not overexpress HER2. Herceptin is indicated for the treatment of patients with HER2 positive localised breast cancer in association with chemotherapy.

Rituximab (MabThera), is a chimeric monoclonal antibody directed against the CD20 protein, that destroys both normal and malignant B cells that have CD20 on their surfaces. It is indicated for non-Hodgkin lymphoma and chronic lymphocytic leukaemia.

Basiliximab (Simulect) is a chimeric mouse-human monoclonal antibody directed against the interleukin-2 (IL-2) receptor found in T cells and is used to prevent rejection in organ transplantation, especially in kidney transplants. It acts as an antagonist at the interleukin-2 binding site of the high affinity IL-2 receptor on the surface of the activated T lymphocytes.