Bill Ruben, Schardt Julian
Universitätsklinik für Medizinische Onkologie, Inselspital, Bern, Schweiz.
Ther Umsch. 2019 Sep;76(4):187-194. doi: 10.1024/0040-5930/a001083.
Immunotherapies - Overview, mode of action and clinical implications The introduction of immunotherapies has led to major advances in the treatment of cancer patients. The mainstays of immunotherapies in clinical routine are immune checkpoint inhibitors. Immune checkpoints like CTLA-4 or the PD-1 / PD-L1 axis are important contributors to the immune homeostasis by preventing overshooting immune responses against pathogens and thus preventing collateral damage to normal tissue, or by preventing autoimmunity. However, immune checkpoints can impede the development of an efficient anti-tumor immune response. Thus, therapeutic monoclonal antibodies against CTLA-4 and PD-1 or PD-L1 displayed remarkable clinical activity such as complete sustained clinical remission even in patients bearing multiple metastases. Malignant melanoma, non-small cell lung cancer or Hodgkin's lymphoma are examples of cancer entities with especially well clinical responses to immune checkpoint inhibitors. This fast-developing field is rapidly expanding the indications for immune checkpoint inhibitors and combinations with other therapeutic strategies like vessel-modulating agents or classical chemotherapy are in preclinical and clinical testing. In this article, the mechanistic principles of immune checkpoint inhibition and their clinical applications are illustrated.
免疫疗法——概述、作用机制及临床意义 免疫疗法的引入使癌症患者的治疗取得了重大进展。临床常规免疫疗法的主要支柱是免疫检查点抑制剂。像CTLA-4或PD-1/PD-L1轴这样的免疫检查点通过防止对病原体的过度免疫反应从而防止对正常组织的附带损害,或者通过预防自身免疫,对免疫稳态起着重要作用。然而,免疫检查点会阻碍有效的抗肿瘤免疫反应的发展。因此,针对CTLA-4和PD-1或PD-L1的治疗性单克隆抗体显示出显著的临床活性,例如即使在患有多处转移的患者中也能实现完全持续的临床缓解。恶性黑色素瘤、非小细胞肺癌或霍奇金淋巴瘤是对免疫检查点抑制剂临床反应特别良好的癌症实体的例子。这个快速发展的领域正在迅速扩大免疫检查点抑制剂的适应症,并且与血管调节药物或经典化疗等其他治疗策略的联合正在进行临床前和临床测试。在本文中,阐述了免疫检查点抑制的机制原理及其临床应用。