Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK; The Royal Marsden Hospital, London, UK.
Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
Trends Immunol. 2014 Jul;35(7):290-8. doi: 10.1016/j.it.2014.05.002. Epub 2014 Jun 18.
Immunomodulatory antibodies influence the direction and magnitude of immune responses against cancer. Significant efficacy has been demonstrated across multiple solid tumour types within clinical trials. Recent preclinical studies indicate that successful outcome relies upon mechanistic activity extending beyond simple receptor stimulation or blockade. In addition to blocking co-inhibitory signals in secondary lymphoid organs, cytotoxic T-lymphocyte antigen (CTLA)-4 antibodies mediate depletion of tumour-infiltrating regulatory T cells by antibody-dependent cellular cytotoxicity (ADCC). This mechanism appears to be common to other immunomodulatory antibodies including those targeting OX40 and glucocorticoid-induced TNFR-related protein (GITR). If verified in the human setting, these findings have significant implications for antibody design, biomarker discovery, and the development of synergistic combinatorial therapies.
免疫调节抗体影响针对癌症的免疫反应的方向和程度。临床试验已经证明了多种实体肿瘤类型的显著疗效。最近的临床前研究表明，成功的结果依赖于超越简单受体刺激或阻断的机制活性。除了在次级淋巴器官中阻断共抑制信号外，细胞毒性 T 淋巴细胞抗原（CTLA）-4 抗体通过抗体依赖性细胞毒性（ADCC）介导肿瘤浸润调节性 T 细胞的耗竭。这种机制似乎与其他免疫调节抗体（包括针对 OX40 和糖皮质激素诱导的 TNFR 相关蛋白（GITR）的抗体）相同。如果在人类环境中得到验证，这些发现对抗体设计、生物标志物发现和协同组合疗法的开发具有重要意义。
