Kobold Sebastian, Krackhardt Angela, Schlösser Hans, Wolf Dominik
Dtsch Med Wochenschr. 2018 Jul;143(14):1006-1013. doi: 10.1055/a-0623-9147. Epub 2018 Jul 13.
Pioneering work has unraveled the role of the immune system in the development and control of cancer. This knowledge has set the basis for the successful implementation of immunotherapy into the standard of care for a large number of cancer types. Based on response rates and prolongation of overall survival, immunotherapeutic approaches have been approved in a growing number of tumor diseases. Activation or therapeutic utilization of T cells represent the basis of these concepts. Checkpoint inhibitory antibodies inhibiting CTLA-4, PD1 and PD-L1 receptors and ligands induce long-term clinical tumor control in a significant number of cancer patients including metastatic melanoma and non-small cell lung cancer. As an alternative concept of T cell activation, the dual CD19 - CD3 targeting bispecific antibody blinatumomab has been approved for refractory acute lymphatic B-cell leukemia (ALL). Moreover, T cells genetically engineered with an anti-CD19-chimeric antigen receptor have also been approved for ALL and malignant B-cell lymphoma by the food and drug administration (FDA). In all of these immunotherapies, severe side effects may occur and require a well-trained team of physicians. Moreover, the growing number of clinically investigated and validated novel compounds as well as cellular therapeutics accentuate the complexity and challenge of this treatment modality. This review highlights the most prominent recent clinical developments in the field of immuno-oncology.
开创性的工作揭示了免疫系统在癌症发生发展及控制中的作用。这一知识为免疫疗法成功纳入多种癌症类型的标准治疗奠定了基础。基于缓解率和总生存期的延长,免疫治疗方法已在越来越多的肿瘤疾病中获得批准。T细胞的激活或治疗性应用是这些概念的基础。抑制CTLA-4、PD1和PD-L1受体及配体的检查点抑制性抗体可在包括转移性黑色素瘤和非小细胞肺癌在内的大量癌症患者中诱导长期临床肿瘤控制。作为T细胞激活的另一种概念,双特异性CD19-CD3靶向抗体blinatumomab已被批准用于难治性急性B淋巴细胞白血病(ALL)。此外,经抗CD19嵌合抗原受体基因工程改造的T细胞也已被美国食品药品监督管理局(FDA)批准用于ALL和恶性B细胞淋巴瘤。在所有这些免疫疗法中,都可能出现严重的副作用,需要训练有素的医生团队。此外,越来越多经过临床研究和验证的新型化合物以及细胞疗法凸显了这种治疗方式的复杂性和挑战性。本综述重点介绍了免疫肿瘤学领域最近最突出的临床进展。