Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma.
Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma.
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从冷冻保存、诱导后化疗、髓母细胞瘤儿科患者的动员白细胞去除术中离体生成树突状细胞。
DOI：
10.1007/s11060-015-1890-2
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发表时间：
2015
影响因子：
3.9
通讯作者：
Mitchell,DuaneA
中科院分区：
文献类型：
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作者：
Nair,SmitaK;Driscoll,Timothy;Boczkowski,David;Schmittling,Robert;Reynolds,Renee;Johnson,LauraA;Grant,Gerald;Fuchs,Herbert;Bigner,DarellD;Sampson,JohnH;Gururangan,Sridharan;Mitchell,DuaneA
患者来源的自体树突状细胞（DC）的产生是用离体产生的负载肿瘤抗原的DC进行癌症免疫治疗的关键组成部分。产生DC的能力的一个重要因素是先前治疗对DC表型和功能的潜在影响。我们研究了使用从患有髓母细胞瘤的儿科患者收获的细胞产生DC的能力，用于在该患者群体中基于DC-RNA的疫苗接种方法的潜在评估。从诱导化疗和粒细胞集落刺激因子动员后的髓母细胞瘤患者白细胞分离术中收获的细胞在用于DC生成之前冷冻保存。使用标准程序从粘附的CD 14+单核细胞产生DC，并分析细胞回收、表型和功能。总之，5名患者中的4名（80%）具有足够的单核细胞恢复以允许DC产生，并且我们能够从这4名患者样品中的3名（75%）产生DC。总的来说，我们成功地从5个患者样品中的3个（60%）产生了符合基于DC的癌症治疗的表型缺陷的DC，并且从5个患者样品中的2个（40%）产生了符合表型和功能缺陷的DC。这项研究强调了从已经用骨髓抑制化疗进行了大量预处理的难治性患者中产生功能性DC用于进一步临床治疗的潜力。在这里，我们证明了评估目前采用的标准护理疗法对癌症患者中基于DC的临床研究的DC离体产生的作用的效用。
Generation of patient-derived, autologous dendritic cells (DCs) is a critical component of cancer immunotherapy with ex vivo-generated, tumor antigen-loaded DCs. An important factor in the ability to generate DCs is the potential impact of prior therapies on DC phenotype and function. We investigated the ability to generate DCs using cells harvested from pediatric patients with medulloblastoma for potential evaluation of DC-RNA based vaccination approach in this patient population. Cells harvested from medulloblastoma patient leukapheresis following induction chemotherapy and granulocyte colony stimulating factor mobilization were cryopreserved prior to use in DC generation. DCs were generated from the adherent CD14+ monocytes using standard procedures and analyzed for cell recovery, phenotype and function. To summarize, 4 out of 5 patients (80 %) had sufficient monocyte recovery to permit DC generation, and we were able to generate DCs from 3 out of these 4 patient samples (75 %). Overall, we successfully generated DCs that met phenotypic requisites for DC-based cancer therapy from 3 out of 5 (60 %) patient samples and met both phenotypic and functional requisites from 2 out of 5 (40 %) patient samples. This study highlights the potential to generate functional DCs for further clinical treatments from refractory patients that have been heavily pretreated with myelosuppressive chemotherapy. Here we demonstrate the utility of evaluating the effect of the currently employed standard-of-care therapies on the ex vivo generation of DCs for DC-based clinical studies in cancer patients.