Adverse events to monoclonal antibodies used for cancer therapy: Focus onhypersensitivity responses.

摘要

Fifteen monoclonal antibodies (mAbs) are currently registered and approved forthe treatment of a range of different cancers. These mAbs are specific for alimited number of targets (9 in all). Four of these molecules are indeed directedagainst the B-lymphocyte antigen CD20; 3 against human epidermal growth factorreceptor 2 (HER2 or ErbB2), 2 against the epidermal growth factor receptor(EGFR), and 1 each against epithelial cell adhesion molecule (EpCAM), CD30, CD52,vascular endothelial growth factor (VEGF), tumor necrosis factor (ligand)superfamily, member 11 (TNFSF11, best known as RANKL), and cytotoxic Tlymphocyte-associated protein 4 (CTLA4). Collectively, the mAbs provoke a widevariety of systemic and cutaneous adverse events including the full range of truehypersensitivities: Type I immediate reactions (anaphylaxis, urticaria); Type II reactions (immune thrombocytopenia, neutopenia, hemolytic anemia); Type IIIresponses (vasculitis, serum sickness; some pulmonary adverse events); and TypeIV delayed mucocutaneous reactions as well as infusion reactions/cytokine releasesyndrome (IRs/CRS), tumor lysis syndrome (TLS), progressive multifocalleukoencephalopathy (PML) and cardiac events. Although the term"hypersensitivity" is widely used, no common definition has been adopted withinand between disciplines and the requirement of an immunological basis for a true hypersensitivity reaction is sometimes overlooked. Consequently, somedrug-induced adverse events are sometimes incorrectly described as"hypersensitivities" while others that should be described are not.