Immunobiology Division, Center of Molecular Immunology, Havana, Cuba.
MAbs. 2011 Nov-Dec;3(6):528-34. doi: 10.4161/mabs.3.6.17770. Epub 2011 Nov 1.
The majority of the most effective monoclonal antibodies (mAbs) currently in the clinics bind to cancer or immune cells. Classic mechanisms of cell killing by therapeutic mAbs include antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and induction of apoptosis by engagement of specific cell ligands. A few reports have described mAbs whose cytotoxic activity is Fc-independent and that do not induce the morphological and biochemical changes associated with the apoptosis-type of cell death. Even fewer works describe mAbs able to directly induce membrane lesions. Here, we discuss the available data on those molecules and their cell killing activity, with particular attention to the case of a mAb specific for the tumor-associated N-glycolyl (Neu5Gc)-GM3 ganglioside (GM3(Neu5Gc)). Some similarities are found in the cell death pathways triggered by these mAbs, but data are not abundant. We conclude that the usefulness of mAbs with a direct cytotoxic activity for immunotherapeutic strategies deserves deeper research.
目前大多数在临床上应用的高效单克隆抗体（mAbs）均能与肿瘤或免疫细胞结合。治疗性 mAbs 通过抗体依赖的细胞介导的细胞毒性、补体依赖的细胞毒性以及与特定细胞配体结合诱导细胞凋亡等经典机制来发挥细胞杀伤作用。少数报道描述了一些不依赖于 Fc 的、不诱导与凋亡型细胞死亡相关的形态和生化变化的 mAbs 具有细胞毒性。更少的工作描述了能够直接诱导膜损伤的 mAbs。在这里，我们讨论了这些分子及其细胞杀伤活性的现有数据，特别关注了针对肿瘤相关 N-糖基化（Neu5Gc）-GM3 神经节苷脂（GM3（Neu5Gc））的 mAb 的情况。这些 mAb 所触发的细胞死亡途径存在一些相似之处，但数据并不丰富。我们得出的结论是，具有直接细胞毒性活性的 mAb 在免疫治疗策略中的应用价值值得进一步研究。
