Ex Vivo IL-15-Stimulated NK Cells as Adoptive Cell Therapy in Haploidentical Transplantation for Pediatric Leukemia

IF 9.9 1区医学 Q1 HEMATOLOGY

American Journal of Hematology Pub Date : 2025-08-08 DOI:10.1002/ajh.70023

Carmen Mestre-Durán, Odelaisy León-Triana, Halin Bareke, Lidia Pertíñez, Laura Clares-Villa, David Bueno, Daniel Lozano-Ojalvo, Alfonso Navarro-Zapata, Luisa Sisinni, Isabel Badell-Serra, Marta González-Vicent, Cristina Beléndez, Pilar Palomo-Moraleda, Yasmina Mozo, Víctor Galán, Mikel Fernández Artázcoz, Carlos Echecopar, Mercedes Gasior, Karima Al-Akioui, Jordi Cano-Ochando, Pilar Guerra-García, María Eugenia Fernández-Santos, Cristina Aguirre-Portolés, Antonio Pérez-Martínez

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Abstract

A Phase I/II clinical trial was conducted in pediatric patients with high-risk malignancies to assess the safety and efficacy of NK cell infusion post-haplo-HSCT. Patients received either alloreactive NK cells from KIR/HLA-mismatched donors or IL-15-stimulated NK cells from KIR/HLA-matched donors, across three dose-escalating cohorts. The IL15-NK cell infusion product demonstrated enhanced activating receptor expression and functional capacity. Increased NKG2D expression was observed in NK cells from patients receiving IL15-NK cells. One-year follow-up showed accelerated immune reconstitution in both the allo-NK and IL15-NK cell arms. IL15-NK recipients exhibited a pro-inflammatory cytokine profile (IL-2, IL-4, IL-6, IFN-γ). Elevated CD69 expression was associated with a higher risk of transplant-related complications.

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体外il -15刺激NK细胞作为儿童白血病单倍体移植的过继细胞疗法

一项针对高危儿童恶性肿瘤患者的I/II期临床试验评估单倍造血干细胞移植后NK细胞输注的安全性和有效性。在三个剂量递增的队列中，患者接受来自KIR/ hla不匹配供者的同种异体反应性NK细胞或来自KIR/ hla匹配供者的il -15刺激NK细胞。il - 15- nk细胞输注产品显示增强激活受体表达和功能能力。在接受IL15-NK细胞治疗的患者NK细胞中观察到NKG2D表达增加。一年的随访显示，在allo-NK和IL15-NK细胞臂中，免疫重建都加快了。il - 15- nk受体表现出促炎细胞因子谱（IL-2、IL-4、IL-6、IFN-γ）。CD69表达升高与移植相关并发症的高风险相关。

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来源期刊

American Journal of Hematology 医学-血液学

CiteScore

15.70

自引率

3.90%

发文量

363

审稿时长

3-6 weeks

期刊介绍： The American Journal of Hematology offers extensive coverage of experimental and clinical aspects of blood diseases in humans and animal models. The journal publishes original contributions in both non-malignant and malignant hematological diseases, encompassing clinical and basic studies in areas such as hemostasis, thrombosis, immunology, blood banking, and stem cell biology. Clinical translational reports highlighting innovative therapeutic approaches for the diagnosis and treatment of hematological diseases are actively encouraged.The American Journal of Hematology features regular original laboratory and clinical research articles, brief research reports, critical reviews, images in hematology, as well as letters and correspondence.