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CAR-CIK 细胞在异基因干细胞移植后复发急性白血病中的治疗潜力

英文原题:Therapeutic Potential of CAR-CIK Cells in Acute Leukemia Relapsed Post Allogeneic Stem Cell Transplantation.

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Therapeutic Potential of CAR-CIK Cells in Acute Leukemia Relapsed Post Allogeneic Stem Cell Transplantation.

PubMed 2025/12/22(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

异体造血干细胞移植(allo-HSCT)后,采用供者来源T细胞进行过继细胞治疗,一直是降低急性髓系和淋巴系白血病复发风险的有吸引力策略。供者淋巴细胞输注(DLI)仍是最成熟的选择,尤其适用于微小残留病(MRD)转阳后的抢先治疗,以及MRD不可检出的预防性治疗。

然而,DLI可能引发移植物抗宿主病(GvHD),限制了其广泛应用。为应对这一挑战,研究者开发了多种替代细胞疗法。其中一种是细胞因子诱导杀伤(CIK)细胞:通过抗CD3抗体、干扰素-γ和白细胞介素-2刺激供者外周血单个核细胞生成。CIK细胞具有兼有T细胞功能与NK样特性的混合表型,并能以不受MHC限制的方式发挥抗肿瘤活性。CIK细胞通常耐受性良好、毒性较低,但迄今疗效有限。基于CAR-T 治疗B细胞淋巴系疾病的经验,研究者将嵌合抗原受体(CAR)工程化导入CIK细胞,形成CAR-CIK细胞。这一新型细胞策略有望用于治疗allo-HSCT后复发的急性髓系及淋巴系白血病。本综述概述CAR-CIK治疗急性白血病的现有经验,并展望其临床转化方向。

展开英文摘要原文

Adoptive cellular therapy with donor-derived T cells has always been an attractive strategy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to reduce the risk of relapse in acute myeloid and lymphoid leukemias. Donor lymphocyte infusion (DLI) is still the best-established option, especially in the preemptive phase when measurable residual disease (MRD) becomes positive and in the prophylactic setting-when MRD is not detectable.

However, the clinical benefit of DLI is counterbalanced by the possible onset of graft-versus-host disease (GvHD), which continues to restrict its wide application. To address this challenge, several alternative cell-based strategies have been developed. One of these is represented by cytokine-induced killer (CIK) cells, generated from donor peripheral blood mononuclear cells through stimulation with anti-CD3 antibodies, interferon- , and interleukin-2. These cells are characterized by a hybrid phenotype, combining T-cell functions with natural killer-like properties, and exhibit antitumor activity in an MHC-unrestricted manner.

CIK cells are generally well tolerated and associated with low toxicity but their efficacy is so far modest. Based on the experience of CAR-T in the treatment of B-cell lymphoid disease, CIK cells have been engineered with chimeric antigen receptors (CAR) developing the CARCIK cells.

This novel cellular strategy represents a promising approach in the treatment of acute myeloid and lymphoid leukemia relapsed post-allo-HSCT. This review provides an overview of the current CAR-CIK experiences in the setting of acute leukemias and outlines future directions for their clinical translation.

论文信息

作者
Canichella M、de Fabritiis P、Abruzzese E
单位
Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy.Italy
文献类型
综述
期刊
Cancers2025 Dec 22
原文标识
PubMed 41514545 · DOI 10.3390/cancers18010032