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靶向 T 细胞恶性肿瘤的嵌合抗原受体细胞治疗

英文原题:Chimeric antigen receptor-based cellular therapy for T-cell malignancies.

查看英文原题

Chimeric antigen receptor-based cellular therapy for T-cell malignancies.

PubMed 2025/11/22(内容时间) Crit Rev Oncol Hematol Q1 · IF 6.2(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法利用合成生物学技术对T细胞进行工程化改造,使其特异性靶向肿瘤细胞,最常用的是通过单链可变片段(scFv)识别肿瘤相关抗原,该疗法已成功应用于B系血液恶性肿瘤患者,包括白血病、淋巴瘤和多发性骨髓瘤。

然而,复发/难治性(R/R)T细胞恶性肿瘤的治疗效果仍不理想。一个重大挑战是恶性T细胞与正常T细胞之间存在共享抗原,导致CAR-T 细胞之间的自相残杀。

此外,患者白细胞分离产物中存在恶性T细胞可能增加复发风险。输注后,患者可能出现严重的T细胞再生障碍,使本就免疫功能低下的癌症患者更加免疫缺陷。本综述探讨了基于CAR的细胞疗法,包括免疫效应细胞(IEC)如常规T细胞亚群、自然杀伤(NK)细胞、自然杀伤T(NKT)细胞、细胞因子诱导的杀伤(CIK)细胞以及用于T细胞恶性肿瘤的T细胞。

我们讨论了多抗原靶向、新兴技术以及最新的临床试验,以期改善针对T系肿瘤的基于CAR的治疗。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapy utilizes synthetic biology techniques to engineer T cells to specifically target tumor cells using most commonly single-chain variable fragments (scFvs) to recognize tumor-associated antigens, which has been successfully applied to patients with B-lineage hematologic malignancies including leukemia, lymphoma and multiple myeloma.

However, treatment outcomes for relapsed or refractory (R/R) T-cell malignancies remain suboptimal. A significant challenge is the shared antigens between malignant and normal T cells, leading to fratricide among CAR T cells.

Moreover, the presence of malignant T cells in patients' leukapheresis may increase risk of relapse. Post-infusion, patients may experience severe T-cell aplasia, rendering the cancer patients who are generally immunocompromised even more immunodeficient. This review article explores CAR-based cellular therapy, including immune effector cells (IECs) such as conventional T cell subsets, natural killer (NK) cells, natural killer T (NKT) cells, cytokine-induced killer (CIK) cells, and T cells for T-cell malignancies.

We discuss multiple antigen-targeting, emerging technologies, and the latest clinical trials in attempt to improve CAR-based therapy for T-lineage neoplasms.

论文信息

作者
Li S、Li Y、Hui MY、Rashid A、Tan HK、Chan S、Chan WYK、Lam KS
第一作者单位
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR. Electronic address: lily123@connect.hku.hk.Hong Kong
通讯作者单位
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR; Children's Blood and Cancer Centre, KK Women's and Children's Hospital, SingHealth Duke-NUS, Singapore. Electronic address: leungwhf@hku.hk.Hong Kong
文献类型
综述
期刊
Critical reviews in oncology/hematology2026 Jan
原文标识
PubMed 41285209 · DOI 10.1016/j.critrevonc.2025.105044