Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Leukemia. 2021 Jul;35(7):1843-1863. doi: 10.1038/s41375-021-01253-x. Epub 2021 May 5.
Acute myeloid leukemia (AML) is a heterogeneous disease linked to a broad spectrum of molecular alterations, and as such, long-term disease control requires multiple therapeutic approaches. Driven largely by an improved understanding and targeting of these molecular aberrations, AML treatment has rapidly evolved over the last 3-5 years. The stellar successes of immunotherapies that harness the power of T cells to treat solid tumors and an improved understanding of the immune systems of patients with hematologic malignancies have led to major efforts to develop immunotherapies for the treatment of patients with AML. Several immunotherapies that harness T cells against AML are in various stages of preclinical and clinical development. These include bispecific and dual antigen receptor-targeting antibodies (targeted to CD33, CD123, CLL-1, and others), chimeric antigen receptor (CAR) T-cell therapies, and T-cell immune checkpoint inhibitors (including those targeting PD-1, PD-L1, CTLA-4, and newer targets such as TIM3 and STING). The current and future directions of these T-cell-based immunotherapies in the treatment landscape of AML are discussed in this review.
急性髓系白血病 (AML) 是一种异质性疾病,与广泛的分子改变有关,因此,长期的疾病控制需要多种治疗方法。在过去的 3-5 年中,AML 的治疗迅速发展,这主要得益于对这些分子异常的理解和靶向治疗的提高。免疫疗法利用 T 细胞的力量来治疗实体瘤取得了巨大成功,以及对血液系统恶性肿瘤患者免疫系统的深入了解,促使人们大力开发免疫疗法来治疗 AML 患者。几种利用 T 细胞对抗 AML 的免疫疗法处于临床前和临床开发的各个阶段。这些包括双特异性和双抗原受体靶向抗体(针对 CD33、CD123、CLL-1 等)、嵌合抗原受体 (CAR) T 细胞疗法以及 T 细胞免疫检查点抑制剂(包括针对 PD-1、PD-L1、CTLA-4 以及 TIM3 和 STING 等新靶点的抑制剂)。本文综述了这些基于 T 细胞的免疫疗法在 AML 治疗领域中的现状和未来发展方向。