利用 3D 胸腺培养系统生成肿瘤抗原特异性 iPSC 衍生的胸腺迁出细胞。
Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System.
机构信息
Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
出版信息
Cell Rep. 2018 Mar 20;22(12):3175-3190. doi: 10.1016/j.celrep.2018.02.087.
Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4CD8 double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs). iTEs exhibit phenotypic and functional similarities to naive T cells both in vitro and in vivo, including the capacity for expansion, memory formation, and tumor suppression. These data illustrate the limitations of current methods and provide a tool to develop the next generation of iPSC-based antigen-specific immunotherapies.
诱导多能干细胞（iPSC）衍生的 T 细胞可能为癌症患者提供未来的治疗方法，但目前的方法（如 OP9/DLL1 系统）产生的 T 细胞存在异常，这对临床转化构成了重大障碍。我们的数据表明，这些 iPSC 衍生的 CD8 单阳性 T 细胞更像是 CD4CD8 双阳性 T 细胞，而不是成熟的 naive T 细胞，因为它们在刺激后表现出发育停滞和先天样表型的表型标志物。我们开发了一种 3D 胸腺培养系统来避免这些异常的发育命运，从而产生了一种称为 iPSC 衍生的胸腺迁出细胞（iTE）的同质 CD8αβ 抗原特异性 T 细胞亚群。iTE 在体外和体内均表现出与 naive T 细胞相似的表型和功能，包括扩增、记忆形成和肿瘤抑制的能力。这些数据说明了当前方法的局限性，并提供了一种开发下一代基于 iPSC 的抗原特异性免疫疗法的工具。
Zotero 插件