Division of Oncology, Department of Medicine, Washington University School of Medicine in St Louis, 660 S. Euclid Ave., St. Louis, MO, USA.
Division of Oncology, Department of Medicine, Washington University School of Medicine in St Louis, 660 S. Euclid Ave., St. Louis, MO, USA.
Best Pract Res Clin Haematol. 2019 Dec;32(4):101097. doi: 10.1016/j.beha.2019.101097. Epub 2019 Oct 18.
At present, the only curative therapy for patients with T-cell malignancies is allogeneic stem cell transplant, which has associated risks and toxicities. Novel agents have been tried in relapsed T-cell acute lymphoblastic leukemia (T-ALL), but only one, with 20%-30% complete remission rates, has been approved by the US Food and Drug Administration. T-ALL is a heterogeneous disease, but it has universal overexpression of CD7 as well as several other T-cell markers, such as CD2 and CD5. T cells engineered to express a chimeric antigen receptor (CAR) are a promising cancer immunotherapy. Such targeted therapies have shown great potential for inducing both remissions and even long-term relapse-free survival in patients with B-cell leukemia and lymphoma. UCART7 for CD7 T-cell malignancies is in development for treatment of relapsed T-ALL in children and adults. It may also have potential in other CD7 hematologic malignancies that lack both effective therapies and targeted therapies. The challenges encountered and progress made in developing a novel fratricide-resistant "off-the-shelf" CAR-T (or UCART7) that targets CD7 T-cell malignancies are discussed here.
目前,T 细胞恶性肿瘤患者唯一的治愈疗法是异基因干细胞移植,但该疗法存在相关风险和毒性。新型药物已在复发性 T 细胞急性淋巴细胞白血病(T-ALL)中进行了尝试,但仅有一种药物(其完全缓解率为 20%-30%)获得了美国食品和药物管理局的批准。T-ALL 是一种异质性疾病,但它普遍过表达 CD7 以及其他几种 T 细胞标志物,如 CD2 和 CD5。表达嵌合抗原受体(CAR)的 T 细胞是一种很有前途的癌症免疫疗法。此类靶向疗法在诱导 B 细胞白血病和淋巴瘤患者缓解甚至长期无复发生存方面显示出巨大潜力。UCART7 用于 CD7 T 细胞恶性肿瘤的开发是为了治疗儿童和成人复发性 T-ALL。它在其他缺乏有效治疗方法和靶向治疗的 CD7 血液恶性肿瘤中也可能具有潜力。本文讨论了开发针对 CD7 T 细胞恶性肿瘤的新型无自相残杀能力“现成”CAR-T(或 UCART7)所面临的挑战和取得的进展。
Best Pract Res Clin Haematol. 2019-10-18
Haematologica. 2024-6-1
Int J Mol Sci. 2024-11-13
Immunotherapy. 2024
Transplant Cell Ther. 2024-6
Blood Adv. 2023-10-24
Cancers (Basel). 2023-2-7
Mol Cancer. 2023-2-16
Biomedicines. 2022-11-13