CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR-T Cells in Acute Myeloid Leukemia: Where Do We Stand?
CAR-T Cells in Acute Myeloid Leukemia: Where Do We Stand?
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
尽管近期取得进展,急性髓系白血病(AML)预后仍不理想,原因包括疾病复发以及对传统和新型疗法产生耐药。表面表达嵌合抗原受体(CAR)的工程化T细胞是最有前景的抗癌药物之一。CAR-T 已越来越多用于B细胞恶性肿瘤并取得显著临床疗效,尽管存在一些免疫相关毒性。然而,目前CAR-T 治疗包括AML在内的髓系肿瘤作用极为有限,因为AML原始细胞通常缺乏免疫细胞可靶向的特异分子。除可安全清除的靶点稀少外,髓系抗原常也表达于正常造血干细胞和祖细胞,靶向后可能造成不可耐受的骨髓清除;AML微环境中的可溶性抑制因子也不利于T细胞增殖。此外,疾病进展迅速进一步增加CAR-T 用于AML的难度。本综述讨论CAR-T 治疗AML现状,包括仍有限的临床证据,以及通过基因改造和联合策略克服局限、使CAR-T 成为有效治疗选择的潜在方法。
Despite recent advances, the prognosis of acute myeloid leukemia (AML) remains unsatisfactory due to disease recurrence and the development of resistance to both conventional and novel therapies. Engineered T cells expressing chimeric antigen receptors (CARs) on their cellular surface represent one of the most promising anticancer agents. CAR-T cells are increasingly used in patients with B cell malignancies, with remarkable clinical results despite some immune-related toxicities.
However, at present, the role of CAR-T cells in myeloid neoplasms, including AML, is extremely limited, as specific molecular targets for immune cells are generally lacking on AML blasts. Besides the paucity of dispensable targets, as myeloid antigens are often co-expressed on normal hematopoietic stem and progenitor cells with potentially intolerable myeloablation, the AML microenvironment is hostile to T cell proliferation due to inhibitory soluble factors.
In addition, the rapidly progressive nature of the disease further complicates the use of CAR-T in AML. This review discusses the current state of CAR-T cell therapy in AML, including the still scanty clinical evidence and the potential approaches to overcome its limitations, including genetic modifications and combinatorial strategies, to make CAR-T cell therapy an effective option for AML patients.
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