Nanoparticle T cell engagers for the treatment of acute myeloid leukemia.
Nanoparticle T cell engagers for the treatment of acute myeloid leukemia.
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DOI：
10.18632/oncotarget.28054
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发表时间：
2021-09-14
期刊：
影响因子：
--
通讯作者：
Azab AK
中科院分区：
文献类型：
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作者：
Alhallak K;Sun J;Muz B;Jeske A;Yavner J;Bash H;Park C;Lubben B;Adebayo O;Achilefu S;DiPersio JF;Azab AK
急性髓性白血病（AML）是最常见的白血病类型，5年生存率为25%。AML的治疗标准在过去几十年中没有改变。正在开发有前途的免疫治疗方案用于治疗AML;然而，这些方案需要非常费力和复杂的技术。我们使用与单克隆抗体偶联的脂质体创建nanoTCE，以实现特异性结合。我们还使用我们的3D培养系统重建了骨髓生态位，并使用免疫功能低下的小鼠，使人类AML和T细胞与nanoTCE一起使用。我们发现CD 33普遍存在于AML细胞上。与同种型相比，CD 33 nanoTCE优先结合AML细胞。我们表明，nanoTCEs有效地激活T细胞，并在体外和体内诱导AML杀伤。我们的研究结果表明，我们的nanoTCE技术是治疗AML的一种新型且有前途的免疫疗法，并为在大型动物和患者中使用nanoTCE的验证提供了补充研究的基础。
Acute myeloid leukemia (AML) is the most common type of leukemia and has a 5-year survival rate of 25%. The standard-of-care for AML has not changed in the past few decades. Promising immunotherapy options are being developed for the treatment of AML; yet, these regimens require highly laborious and sophisticated techniques. We create nanoTCEs using liposomes conjugated to monoclonal antibodies to enable specific binding. We also recreate the bone marrow niche using our 3D culture system and use immunocompromised mice to enable use of human AML and T cells with nanoTCEs. We show that CD33 is ubiquitously present on AML cells. The CD33 nanoTCEs bind preferentially to AML cells compared to Isotype. We show that nanoTCEs effectively activate T cells and induce AML killing in vitro and in vivo. Our findings suggest that our nanoTCE technology is a novel and promising immuno-therapy for the treatment of AML and provides a basis for supplemental investigations for the validation of using nanoTCEs in larger animals and patients.