脐带血源性产品Omidubicel的临床研发进展

doi:10.3877/cma.j.issn.2095-1221.2023.03.008

中华细胞与干细胞杂志(电子版) ›› 2023, Vol. 13 ›› Issue (03) : 178 -182. doi: 10.3877/cma.j.issn.2095-1221.2023.03.008

综述

脐带血源性产品Omidubicel的临床研发进展

崔燕妮, 任颜, 梁凤婷, 覃艳红, 王宏伟^†(

)

030001　太原，山西医科大学第二医院血液病研究所；030001　太原，血液病分子诊疗山西省重点实验室；030001　太原，山西省干细胞临床转化研发联合实验室
030001　太原，山西医科大学第二医院血液病研究所；030001　太原，血液病分子诊疗山西省重点实验室

收稿日期:2023-03-09 出版日期:2023-06-01
通信作者: 王宏伟
基金资助:
山西省中央引导地方科技发展资金项目(YDZJSX2021B009); 山西省医学重点科技项目计划(2021XM07)

Clinical research and development progress of cord blood-derived product Omidubicel

Yanni Cui, Yan Ren, Fengting Liang, Yanhong Tan, Hongwei Wang^†()

Institute of Hematology of the Second Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Molecular Diagnosis and Treatment of Hematology Diseases, Taiyuan 030001, China; Joint Laboratory of Stem Cell Clinical Transformation and Research in Shanxi Province, Taiyuan 030001, China
Institute of Hematology of the Second Hospital of Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Molecular Diagnosis and Treatment of Hematology Diseases, Taiyuan 030001, China

Received:2023-03-09 Published:2023-06-01
Corresponding author: Hongwei Wang

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引用本文：

崔燕妮, 任颜, 梁凤婷, 覃艳红, 王宏伟. 脐带血源性产品Omidubicel的临床研发进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(03): 178-182.

Yanni Cui, Yan Ren, Fengting Liang, Yanhong Tan, Hongwei Wang. Clinical research and development progress of cord blood-derived product Omidubicel[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(03): 178-182.

作为造血干细胞（HSC）的重要来源之一，脐带血的临床应用受到CD34⁺细胞剂量低、造血恢复缓慢和移植失败风险增加的限制。Omidubicel是利用烟酰胺（NAM）进行HSC体外扩增的脐带血细胞治疗产品，在同种异体HSC移植中比未经处理的脐带血植入速度更快，感染率更低。本文重点回顾Omidubicel在恶性血液病中的临床应用，总结该扩增策略的早期益处，但其对患者的长期影响仍需要大规模的临床研究进行观察。总而言之，Omidubicel的出现将扩增脐带血移植推向了移植治疗和再生医学的前沿。

关键词: Omidubicel, 脐带血, 造血干细胞, 体外扩增, 烟酰胺

The clinical application of umbilical cord blood as a source of hematopoietic stem cells (HSC) for transplantation is limited by the low dose of CD34⁺ cells, increased risk of graft failure and slow hematopoietic recovery. Omidubicel is a kind of Umbilical cord blood cell therapy product that expands hematopoietic stem cells in vitro by nicotinamide (NAM) . Compared with unmanipulated Umbilical cord blood, it has faster implantation speed and a lower infection rate in allogeneic hematopoietic stem cell transplantation. Here, we focus on reviewing the relevant data on the clinical application of Omidubicel in malignant hematological diseases, and affirm the early benefits of this amplification strategy. However, its long-term impact on patients still requires large-scale clinical studies. The emergence of Omidubicel pushes expanded umbilical cord blood transplantation to the forefront of transplantation treatment and regenerative medicine.

Key words: Omidubicel, Umbilical cord blood, Hematopoietic stem cells, In vitro expansion, Nicotinamide

图1 烟酰胺抑制SIRT1脱乙酰化反应注：Ac为乙酰基；Tyr为酪氨酸；NAD+为烟酰胺腺嘌呤二核苷酸；NAM为烟酰胺

图2 Omidubicel的制备流程

表1 Omidubicel相关临床试验数据

	CD34⁺细胞扩增倍数	CD34⁺细胞回输数量/ （×10⁶/kg）	中性粒细胞植入中位时间（d）	血小板植入中位时间（d）	100 d a-GVHD
Ⅰ期临床试验^[16]	72	3.5	13（25^*）	33（37^*）	45.5%
Ⅰ/Ⅱ期临床试验^[17]	33	6.3	11.5（21^*）	34（46^*）	44% （56%^*）
Ⅲ期临床试验^[18]	130	9.0	12（22^*）	37（50^*）	56% （43%^*）
	100 d Ⅲ-Ⅳa-GVHD	2年c-GVHD	2年OS率	2年PFS率	住院天数（d）
Ⅰ期临床试验^[16]	0	18.2%	82%^#	73%^#	26
Ⅰ/Ⅱ期临床试验^[17]	11% （27%^*）	40% （30%^*）	51% （48%^*）	43% （45%^*）	20
Ⅲ期临床试验^[18]	14% （21%^*）	35% （29%^*）	n.a	36%（45%^*）	27（35^*）

表1 Omidubicel相关临床试验数据

	CD34⁺细胞扩增倍数	CD34⁺细胞回输数量/ （×10⁶/kg）	中性粒细胞植入中位时间（d）	血小板植入中位时间（d）	100 d a-GVHD
Ⅰ期临床试验^[16]	72	3.5	13（25^*）	33（37^*）	45.5%
Ⅰ/Ⅱ期临床试验^[17]	33	6.3	11.5（21^*）	34（46^*）	44% （56%^*）
Ⅲ期临床试验^[18]	130	9.0	12（22^*）	37（50^*）	56% （43%^*）
	100 d Ⅲ-Ⅳa-GVHD	2年c-GVHD	2年OS率	2年PFS率	住院天数（d）
Ⅰ期临床试验^[16]	0	18.2%	82%^#	73%^#	26
Ⅰ/Ⅱ期临床试验^[17]	11% （27%^*）	40% （30%^*）	51% （48%^*）	43% （45%^*）	20
Ⅲ期临床试验^[18]	14% （21%^*）	35% （29%^*）	n.a	36%（45%^*）	27（35^*）

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