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优化肿瘤相关抗原刺激的自体树突状细胞与细胞因子诱导的杀伤细胞共培养以增强癌症免疫治疗中的细胞毒性

英文原题:Optimizing tumor-associated antigen-stimulated autologous dendritic cell and cytokine-induced killer cell coculture to enhance cytotoxicity for cancer immunotherapy in manufacturing.

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Optimizing tumor-associated antigen-stimulated autologous dendritic cell and cytokine-induced killer cell coculture to enhance cytotoxicity for cancer immunotherapy in manufacturing.

PubMed 2023/06/29(内容时间) BMC Immunol Q3 · IF 2.9(JCR 2025)

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研究概要

体外实验显示,当共培养中 DC-CIK 细胞比例为 1:20 时,CIK 细胞在第 14 天分泌的细胞因子数量最高,抗肿瘤免疫效果最强。当 CIK:K562 细胞比例为 25:1 时,CIK 细胞对 K562 细胞的细胞毒性最高。我们开发了 DC-CIK 共培养的高效制备工艺,同时确定了免疫活性的最佳 DC-CIK 细胞比例和最佳细胞毒性 CIK:K562 细胞比例。

研究思路结论见上方概要

树突状细胞-细胞因子诱导的杀伤细胞(DC-CIK)共培养治疗在肿瘤免疫治疗中已显示出有效性。然而,DC-CIK治疗的费用对许多患者而言过于高昂,且缺乏标准化的制备工艺和治疗策略是主要限制。我们的研究使用肿瘤裂解物作为肿瘤相关抗原来源,并将DCs与CIK细胞共培养。我们开发了一种从外周血中获取自体DCs和CIK细胞的高效方法。我们使用流式细胞术评估DC活化,并使用细胞计数珠阵列法检测CIK细胞分泌的细胞因子。

我们在体外用K562细胞系评估了DC-CIK共培养的抗肿瘤活性。我们证明,采用冷冻未成熟DC的生产工艺可以实现最低损失和最高经济效益。在肿瘤相关抗原存在的情况下,DC-CIK共培养可以有效提升CIK细胞对肿瘤的免疫特异性。

展开英文摘要原文

Dendritic Cell Cytokine-induced killer cell (DC-CIK) coculture treatment in cancer immunotherapy has been shown to be effective. However, the cost of DC- CIK therapy is prohibitive for many patients, and the lack of standard manufacturing processes and treatment strategies are major limitations. Our study used tumor lysate as a tumor-associated antigen source and DCs and CIK cells in coculture. We developed an efficient method to obtain autologous DCs- and CIK cells from peripheral blood. We used flow cytometry to assess DC activation and the cytometric bead array assay to quantify cytokines secreted by CIK cells.

We evaluated the antitumor activity of DC- CIK coculture in vitro with the K562 cell line. We demonstrated that a manufacturing process employing frozen immature DCs can yield the lowest loss with the highest economic benefits. DC-CIK coculture can effectively upgrade CIK cells' immunological specificity to tumors in the presence of tumor-associated antigens.

In vitro experiments revealed that when the DC- CIK cell ratio was 1: 20 in the coculture, CIK cells secreted the highest number of cytokines on the 14th day and the antitumor immune effect showed the highest potency. CIK cells' cytotoxicity to K562 cells was highest when the CIK: K562 cell ratio was 25: 1. We developed an efficient manufacturing process for DC- CIK coculture, while also establishing the optimal DC- CIK cell ratio for immunological activity and the best cytotoxic CIK: K562 cell ratio.

论文信息

作者
Lee YY、Luo SC、Lee CH、Tang CL、Shen CC、Cheng WY、Yang YC、Yang MY
第一作者单位
Division of Pediatric Neurosurgery, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.Taiwan
通讯作者单位
Department of Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan. chunmingyen@gmail.com.Taiwan
期刊
BMC immunology2023 Jun 29
原文标识
PubMed 37386444 · DOI 10.1186/s12865-023-00552-5