CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
Kit-M（GM-CSF 和 PGE-1）与 Kit-I（GM-CSF 和 Picibanil）用于生成 DCs/DCleus 及其对后续体外抗白血病免疫细胞激活影响的比较评价
英文原题：Comparative Evaluation of Kit-M (GM-CSF and PGE-1) and Kit-I (GM-CSF and Picibanil) for the Generation of DCs/DCleus and Their Impact on Subsequent Antileukemic Immune Cell Activation Ex Vivo.
查看英文原题
Comparative Evaluation of Kit-M (GM-CSF and PGE-1) and Kit-I (GM-CSF and Picibanil) for the Generation of DCs/DCleus and Their Impact on Subsequent Antileukemic Immune Cell Activation Ex Vivo.
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中文摘要
我们通过量化以下内容比较了Kit-I与Kit-M的效果：（1）它们从6名健康个体和28名处于不同疾病阶段的AML患者WB样本中产生DCs/DCleus的潜力；（2）在与经或未经Kit-I/Kit-M预处理的WB进行MLC后，适应性和固有白血病特异性产生IFNγ或脱颗粒的抗白血病细胞的激活情况。此外，我们将所得结果与所获得的细胞抗白血病功能改善以及患者临床数据进行相关性分析。
在AML样本中，我们发现，与未处理样本相比，经Kit-M处理以及经Kit-I处理（尽管较不显著）的样本中，能够在不诱导原始细胞增殖的情况下生成的（成熟）DCleus频率显著更高，（白血病特异性）免疫反应性细胞频率显著增加，并且在经Kit-M和经Kit-I处理样本与未处理样本相比的MLC后，原始细胞细胞毒性改善（可能在经Kit-I预处理样本中CD4和CIK IFNγ+细胞的诱导更高）。这些数据可能提示，两种Kit通过不同途径发挥作用。
我们表明，Kit-M和Kit-I可产生DCs/DCleus，并随后（可能通过不同的作用方式）增强MLC后的抗白血病免疫细胞激活。我们的发现提示，通过联合用药或在个体化治疗过程中为相应患者确定选择合适药物（组合）的标准，有可能增强体内抗白血病治疗的效果。
展开英文摘要原文
Background /Objectives : Novel (immune) therapies are needed to stabilize the disease or achieve remissions in AML.
We already demonstrated that DCleus can be generated ex vivo from AML patients' blasts in WB using approved drugs (GM-CSF and PGE-1 (Kit-M) or GM-CSF and Picibanil (OK-432), Kit-I). The generated DCleus induce antileukemia-directed immune cells of the adaptive and innate immune system, enabling leukemia-specific immune activation after MLC.
Methods : We compared the effects of Kit-I vs. Kit-M by quantifying (1) their potential to produce DCs/DCleus from WB samples from 6 healthy individuals and 28 AML patients' WB in different stages of the disease and (2) the activation of adaptive and innate leukemia-specific IFNγ-producing or degranulating antileukemic cells after MLC with and without Kit-I/Kit-M-pretreated WB.
Furthermore, we correlated the obtained results with the achieved improved cells' antileukemic functionality and patients' clinical data. Results : In AML samples we found significantly higher frequencies of (mature) DCleus generable without induction of blast proliferation in Kit-M as well as (although less pronounced) in Kit-I-treated vs. untreated samples, a significant increase in the frequency of (leukemia- specific) immunoreactive cells, and improved blast cytotoxicity after MLC with Kit-M and with Kit-I-treated vs.
untreated samples (potentially with higher induction of CD4 and CIK IFNγ + cells in Kit-I-pretreated samples). These data might suggest that both Kits work via different pathways. Conclusions : We show that Kit-M and Kit-I produce DCs/DCleus and subsequently enhance (potentially via a different mode of action) antileukemic immune cell activation after MLC.
Our findings point to a possibility to enhance antileukemic treatment in vivo by combining agents or identifying criteria for selecting an appropriate agent (combination) for the respective patient in the course of a personalized treatment strategy.
论文信息
- 作者
- Deen D、Schutti O、Baudrexler T、Amberger DC、Plett C、Klauer L、Schmohl J、Bojko P
- 单位
- Department of Medicine III, University Hospital of Ludwig-Maximilian-University Munich, 81377 Munich, Germany.Germany
- 期刊
- Cancers2026 Aug 23
- 原文标识
- PubMed 42738251 · DOI 10.3390/cancers18172729
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