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一种由 NK 细胞和γδ T 细胞组成的新型 GMP 生产候选药物,作为造血干细胞移植的辅助免疫治疗

英文原题:A novel GMP-manufactured medicinal product candidate composed of NK and γδ T cells as adjunct immunotherapy for hematopoietic stem cell transplantation.

PubMed 2026/02/28(内容时间) Cell Transplant Q2 · IF 3.7(JCR 2025)

研究概要

我们实施了一种新的ATMP,不久将转化为临床实践,该疗法可能在移植后阶段作为有效的免疫疗法用于神经母细胞瘤和白血病儿科患者。

中文摘要

γδ T 淋巴细胞和 NK 细胞能有效杀伤肿瘤或病毒感染细胞,同时避免移植物抗宿主病(GvHD),因此作为过继性细胞治疗的潜在工具引起了高度关注。我们制备了一种由成熟 γδ T 和 NK 细胞组成的先进治疗药品(ATMP),旨在提供一种创新工具,保护患者免受单倍体相合造血干细胞移植后的肿瘤复发和危及生命的感染。该 ATMP 在 GMP 设施中生产并验证,来源于经唑来膦酸和 IL-2 刺激的白细胞单采产物,随后使用 CliniMACS Prodigy 去除 αβ T 淋巴细胞。该 ATMP 具有高度均一性、细胞活力、细胞毒能力、低温保存后的稳定性,并且几乎不含 αβ T 和 B 淋巴细胞。NK 和 γδ T 细胞均被激活,并以高表达细胞毒性和活化性受体为特征,包括 NKG2D、CD16、NKp30、NKp44 和 NKp46。此外,γδ T 淋巴细胞和 NK 细胞对髓系白血病或神经母细胞瘤细胞具有细胞毒性。总之,我们实现了一种新型 ATMP,可望很快转化为临床实践,可在移植后阶段作为神经母细胞瘤和白血病儿科患者的有效免疫治疗。

展开英文摘要原文

γδ T lymphocytes and NK cells are effective to kill tumors or viral-infected cells avoiding graft versus host disease (GvHD), thus they have attracted high interest as potential tool for adoptive cell therapy. We generated an advanced therapy medicinal product (ATMP) composed of mature γδ T and NK cells to provide an innovative tool to protect patients against tumor relapse and life-threatening infection after haploidentical hematopoietic stem cell transplantation. The ATMP was manufactured and validated in a GMP facility and was obtained from leukapheresis stimulated with zoledronic acid and IL-2, afterward depleted of αβ T lymphocytes using the CliniMACS Prodigy. The ATMP is characterized by high homogeneity, cell viability, cytotoxic abilities, stability after cryogenic preservation, and it was virtually free of αβ T and B lymphocytes. Both NK and γδ T cells were activated and characterized by high expression of cytotoxic and activating receptors including NKG2D, CD16, NKp30, NKp44, and NKp46. Furthermore, γδ T lymphocytes and NK cells were cytotoxic against myeloid leukemia or neuroblastoma cells. In conclusion, we implemented a novel ATMP to be shortly translated into clinical practice, which may be used in the post-transplant phase as efficacious immunotherapy in neuroblastoma and leukemic pediatric patients.

论文信息

作者
Morandi F、Della Lastra M、Tripodi G、Sabatini F、Cocco C、Risso M、Gramignoli R、Zara F
单位
UOSD Laboratorio Terapie Cellulari, Dipartimento dei Servizi, IRCCS Istituto Giannina Gaslini, Genova, Italy.Italy
文献类型
非美国政府资助研究
期刊
Cell transplantation2026 Jan-Dec
原文标识
PubMed 41761987 · DOI 10.1177/09636897251374248