Biologics

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.