Currently, ~28–30 mAbs are approved or under consideration for approval as specific therapies in the USA or European Union, although about 350 new mAbs for therapeutic application in humans are in the commercial pipeline. So far, the number of target antigens for the mAbs is surprisingly small with more than one of the approved antibodies specific for TNF, HER2, CD20, EGFR, or VEGF. Other specificities include EpCAM, glycoprotein IIb/IIIa, CD30, CD52, C5, α-4 integrin, IgE, IL-6R, BLys, IL-1β, and RANK-L. Initial infusion reactions to some mAbs may provoke tumor lysis syndrome, cytokine release syndrome, and systemic inflammatory response syndrome. Systemic and cutaneous reactions also occur to mAbs. Rituximab, for example, may cause serum sickness, vasculitis, cutaneous reactions, interstitial pneumonitis, and ARDS as well as post-infusion reactions. Some patients receiving cetuximab experienced severe immediate hypersensitivity reactions. The antibodies involved are IgE specific for α-d-galactose-(1–3)-β-d-galactose and reactive with this disaccharide present on the Fab portion of the chimeric antibody. The nature of, and main adverse reactions to, etanercept, the synthetic IFNs pegylated IFNα-2a and pegylated IFNα-2b, IL-2, denileukin diftitox, anakinra, aflibercept, anti-thymocyte globulin, epoetins, and recombinant human insulin are discussed.
Fleischmann RM, Tesser J, Schiff MH, et al. Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann Rheum Dis. 2006; 65:6–12.Google Scholar
Foss FM, Bacha P, Osann KE, et al. Biological correlates of acute hypersensitivity events with DAB389IL-2 (denileukin diftitox, Ontak®) in cutaneous T-cell lymphoma: Decreased frequency and severity with steroid premedication. Clin Lymphoma. 2001;1: 298–302.PubMedCrossRefGoogle Scholar
Hansel TT, Kropshofer H, Singer T, et al. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov. 2010;9:325–38.PubMedCrossRefGoogle Scholar
Kaneko E, Niwa R. Optimizing therapeutic antibody function: progress with Fc domain engineering. BioDrugs. 2011;25:1–11.PubMedCrossRefGoogle Scholar
Li J, Zhu Z. Research and development of next generation of antibody-based therapeutics. Acta Pharmacol Sin. 2010;31:1198–207.PubMedCrossRefGoogle Scholar
Shim H. One target, different effects: a comparison of distinct therapeutic antibodies against the same targets. Exp Mol Med. 2011;43:539–49.PubMedCrossRefGoogle Scholar
Winkler U, Jensen M, Manzke O, et al. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood. 1999;94:2217–24.PubMedGoogle Scholar