Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia.
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Curr Opin Pediatr. 2018 Feb;30(1):25-29. doi: 10.1097/MOP.0000000000000572.
Immunotherapy for the treatment of cancer has advanced at a tremendous pace over the last decade. In this review, we provide an overview of recent progress in immunotherapy for the treatment of leukemia, focusing on antibody-drug conjugates (ADC), bi-specific T-cell engagers (BiTE), and chimeric antigen receptor (CAR) T cells.
Ongoing clinical trials of CAR T cells directed against CD19 have produced complete remission rates as high as 93%, prompting global multicenter phase 2 trials and the first FDA approval of a CAR T-cell therapy. Insights into cytokine release syndrome, a toxicity of CAR T-cell therapy, and the cause for relapse after CAR T-cell therapy are evolving. The bispecific antibody blinatumomab and the ADCs inotuzumab and gemtuzumab have also recently received FDA approval for ALL and AML, respectively, moving these agents into a more prominent role in the relapse setting.
The use of immunotherapy for leukemia has been successful in creating durable remissions for multiply relapsed and refractory patients who previously had little chance of cure. The ongoing clinical and preclinical work continues to advance our understanding of these immune-based therapies, and will shape the next generation of clinical trials.
目的综述:在过去的十年中,癌症的免疫疗法取得了飞速的发展。在这篇综述中,我们概述了针对白血病的免疫疗法的最新进展,重点介绍了抗体药物偶联物(ADC)、双特异性 T 细胞衔接器(BiTE)和嵌合抗原受体(CAR)T 细胞。
最新发现:针对 CD19 的 CAR T 细胞的临床试验持续进行,完全缓解率高达 93%,促使全球多中心 2 期临床试验和首个 FDA 批准的 CAR T 细胞疗法。人们对细胞因子释放综合征(CAR T 细胞疗法的一种毒性)和 CAR T 细胞治疗后复发的原因的认识不断发展。双特异性抗体blinatumomab 和 ADCs inotuzumab 和 gemtuzumab 也分别最近获得 FDA 批准用于 ALL 和 AML,使这些药物在复发环境中发挥更重要的作用。
总结:免疫疗法在治疗复发性和难治性白血病患者方面取得了成功,这些患者以前几乎没有治愈的机会。正在进行的临床前和临床工作继续推进我们对这些免疫疗法的理解,并将为下一代临床试验提供指导。