Division of Hematological Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Division of Hematology and Medical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
Br J Haematol. 2021 Dec;195(5):660-668. doi: 10.1111/bjh.17544. Epub 2021 May 25.
Chimeric antigen receptor (CAR) T-cell therapy has brought a paradigm shift in the management of haematological malignancies and has opened novel avenues of investigational therapeutic strategies. Given these encouraging responses, it has become imperative to understand the full spectrum of biology and potential toxicities that can arise from these novel agents, as well as those under investigation. With the increasing use of CAR T-cell therapy for relapse following allogeneic haematopoietic cell transplantation (HCT) and the imminence of allogeneic CAR T cells, risks from T cell-based therapy, such as the previously well-recognised graft-versus-host disease (GVHD), have gained prominence and warrant explanation. In the present review, we discuss the risk of GVHD in the: (1) post-HCT setting using recipient or donor-derived CAR T cells, as well as (2) non-HCT setting using autologous, as well as allogeneic T-cell therapies. A better understanding of this risk is important to advance the field and ensure safe development and use of these agents in the clinic.
嵌合抗原受体 (CAR) T 细胞疗法在血液系统恶性肿瘤的治疗中带来了范式转变,并为探索治疗策略开辟了新途径。鉴于这些令人鼓舞的反应,了解这些新型药物以及正在研究中的药物的生物学全貌和潜在毒性变得至关重要。随着 CAR T 细胞疗法在同种异体造血细胞移植 (HCT) 后复发中的应用越来越多,以及同种异体 CAR T 细胞的出现,基于 T 细胞的治疗的风险,如先前公认的移植物抗宿主病 (GVHD),已引起关注,并需要加以解释。在本综述中,我们讨论了 GVHD 的风险:(1) 使用受者或供者来源的 CAR T 细胞在 HCT 后,以及 (2) 使用自体和同种异体 T 细胞疗法在非 HCT 中。更好地了解这种风险对于推进该领域以及确保这些药物在临床中的安全开发和使用非常重要。