CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
使用 Idelalisib 增强双阴性 T 细胞对急性髓系白血病的治疗疗效
英文原题：Enhancing Therapeutic Efficacy of Double Negative T Cells against Acute Myeloid Leukemia Using Idelalisib.
查看英文原题
Enhancing Therapeutic Efficacy of Double Negative T Cells against Acute Myeloid Leukemia Using Idelalisib.
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中文摘要
双阴性T细胞（DNT）是一种独特的T细胞亚群，具有强大的抗白血病潜力。此前，DNT疗法已被证明能在患者来源的异种移植（PDX）模型中有效靶向AML细胞。此外，最近完成的一项I/IIa期临床研究证明了其在异基因造血干细胞移植后复发的AML患者中的安全性、可行性和潜在疗效。然而，DNT介导的抗白血病反应的持久性和持续性尚不十分清楚。在本研究中，我们表征了DNT在PDX模型中的体内持久性。此外，我们通过磷酸肌醇3-激酶δ（PI3Kδ）抑制提高了DNT介导活性的疗效和持久性。在机制上，用PI3Kδ抑制剂Idelalisib（Ide）处理的DNT表现出早期记忆表型，具有更优的活力和增殖能力，但细胞耗竭更少。总体而言，本研究的发现支持使用Ide处理的DNT来改善其治疗结局。
展开英文摘要原文
The double negative T cell (DNT) is a unique subset of T cells with potent anti-leukemic potential. Previously, DNT therapy has been shown to effectively target AML cells in patient-derived xenograft (PDX) models.
Further, a recently completed phase I/IIa clinical study demonstrated the safety, feasibility, and potential efficacy in AML patients that relapsed after allogeneic hematopoietic stem cell transplantation.
However, the persistence and durability of DNT-mediated anti-leukemic response is less well understood. In this study, we characterized the in vivo persistence of DNTs in PDX models.
Further, we improved the efficacy and durability of DNT-mediated activity with phosphoinositide 3-kinase delta (PI3Kδ) inhibition.
Mechanistically, DNTs treated with the PI3Kδ inhibitor, Idelalisib (Ide), exhibited early memory phenotype with superior viability and proliferative capacity but less cell exhaustion. Collectively, the findings from this study support the use of Ide-treated DNTs to improve its therapeutic outcome.
论文信息
- 作者
- Kang H、Lee JB、Khatri I、Na Y、D'Souza C、Arruda A、Minden MD、Zhang L
- 单位
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada.Canada
- 期刊
- Cancers2021 Oct 9
- 原文标识
- PubMed 34680188 · DOI 10.3390/cancers13205039
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