Baldo Brian A
Molecular Immunology Unit; Kolling Institute of Medical Research; Royal North Shore Hospital of Sydney; Sydney, Australia ; Department of Medicine; University of Sydney; Sydney, Australia.
Oncoimmunology. 2013 Oct 1;2(10):e26333. doi: 10.4161/onci.26333. Epub 2013 Oct 17.
Fifteen monoclonal antibodies (mAbs) are currently registered and approved for the treatment of a range of different cancers. These mAbs are specific for a limited number of targets (9 in all). Four of these molecules are indeed directed against the B-lymphocyte antigen CD20; 3 against human epidermal growth factor receptor 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 T lymphocyte-associated protein 4 (CTLA4). Collectively, the mAbs provoke a wide variety of systemic and cutaneous adverse events including the full range of true hypersensitivities: Type I immediate reactions (anaphylaxis, urticaria); Type II reactions (immune thrombocytopenia, neutopenia, hemolytic anemia); Type III responses (vasculitis, serum sickness; some pulmonary adverse events); and Type IV delayed mucocutaneous reactions as well as infusion reactions/cytokine release syndrome (IRs/CRS), tumor lysis syndrome (TLS), progressive multifocal leukoencephalopathy (PML) and cardiac events. Although the term "hypersensitivity" is widely used, no common definition has been adopted within and between disciplines and the requirement of an immunological basis for a true hypersensitivity reaction is sometimes overlooked. Consequently, some drug-induced adverse events are sometimes incorrectly described as "hypersensitivities" while others that should be described are not.
目前有15种单克隆抗体(mAb)已注册并获批用于治疗一系列不同的癌症。这些单克隆抗体针对的靶点数量有限(总共9个)。其中4种分子确实是针对B淋巴细胞抗原CD20;3种针对人表皮生长因子受体2(HER2或ErbB2),2种针对表皮生长因子受体(EGFR),还有1种分别针对上皮细胞粘附分子(EpCAM)、CD30、CD52、血管内皮生长因子(VEGF)、肿瘤坏死因子(配体)超家族成员11(TNFSF11,最广为人知的是RANKL)和细胞毒性T淋巴细胞相关蛋白4(CTLA4)。总的来说,这些单克隆抗体引发了各种各样的全身和皮肤不良事件,包括所有类型的真正超敏反应:I型即刻反应(过敏反应、荨麻疹);II型反应(免疫性血小板减少症、中性粒细胞减少症、溶血性贫血);III型反应(血管炎、血清病;一些肺部不良事件);以及IV型迟发性黏膜皮肤反应,还有输液反应/细胞因子释放综合征(IRs/CRS)、肿瘤溶解综合征(TLS)、进行性多灶性白质脑病(PML)和心脏事件。尽管“超敏反应”一词被广泛使用,但各学科内部和之间尚未采用共同的定义,而且真正的超敏反应的免疫学基础要求有时被忽视。因此,一些药物引起的不良事件有时被错误地描述为“超敏反应”,而其他一些应该被描述为超敏反应的却没有。
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