Brentuximab vedotin is an antibody-drug conjugate that binds CD30, a cell surface marker in the TNF receptor superfamily that is expressed on anaplastic large T-cell lymphomas and on Reed-Sternberg cells in Hodgkin’s lymphoma; it may also be expressed on activated leukocytes. Brentuximab vedotin consists of a chimeric (mouse-human) IgG1 linked to monomethylauristatin E (MMAE), a microtubule-disrupting agent that induces cell cycle arrest and apoptosis. When this ADC binds CD30 on the cell surface, the complex is internalized followed by proteolytic cleavage of MMAE from the IgG. Brentuximab is approved for treatment of patients with Hodgkin’s lymphoma after failure of autologous stem cell transplantation or after failure of at least two previous chemotherapy regimens. It is also approved for patients with systemic anaplastic large cell lymphoma after failure of at least one previous multiagent chemotherapy regimen. Patients taking brentuximab vedotin should be monitored primarily for neutropenia and peripheral sensory neuropathy.
Capromab pendetide is a murine monoclonal antibody specific for prostate specific membrane antigen. It is coupled to isotopic indium (111In) and is used in immunoscintigraphy for patients with biopsy-confirmed prostate cancer and post-prostatectomy in patients with rising prostate-specific antibody level to determine extent of disease.
Ibritumomab tiuxetan is an anti-CD20 murine monoclonal antibody labeled with isotopic yttrium (90Y) or 111In. The radiation of the isotope coupled to the antibody provides the major antitumor activity of this drug. Ibritumomab is approved for use in patients with relapsed or refractory low-grade, follicular, or B-cell non-Hodgkin’s lymphoma, including patients with rituximab-refractory follicular disease. It is used in conjunction with rituximab in a two-step therapeutic regimen.
Mabs and Fusion Proteins Used as Immunomodulatory & Anti-Inflammatory Agents
Adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab are antibodies that bind and neutralize the biological activity of TNF-α, a proinflammatory cytokine that is important in adult and juvenile rheumatoid arthritis and similar inflammatory diseases such as psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis.
Abatacept and belatacept are recombinant fusion proteins composed of the extracellular domain of cytotoxic T-lymphocyteassociated antigen 4 (CTLA-4) fused to the Fc domains of human IgG1 (Figure 55–7). Abatacept is approved for use in rheumatoid and other forms of arthritis and is discussed in Chapter 36. Belatacept is approved to help prevent rejection in kidney transplants. Both fusion proteins block the activation of T cells by binding CD80, blocking the CD28 activation signal in T cells.
Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist that prevents IL-1 from binding to its receptor, stemming the cascade of cytokines that would otherwise be released. Anakinra is approved for use in adult rheumatoid arthritis patients who have failed treatment with one or more disease-modifying anti-rheumatic drugs. Rilonacept is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human interleukin-1 receptor component (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP) fused to the Fc portion of human IgG1. These molecules are indicated for treatment of cryopyrinassociated periodic syndromes.