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增强型细胞因子诱导的杀伤细胞作为肾细胞癌辅助免疫治疗的疗效:临床前和临床研究。

Efficacy of Enhanced Cytokine-Induced Killer Cells as an Adjuvant Immunotherapy for Renal Cell Carcinoma: Preclinical and Clinical Studies.

机构信息

Central Laboratory of Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan Province, China.

Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, Yunnan Province, China.

出版信息

J Healthc Eng. 2021 Sep 8;2021:5709104. doi: 10.1155/2021/5709104. eCollection 2021.

DOI:10.1155/2021/5709104
PMID:34540187
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8443387/
Abstract

Cytokine-induced killer (CIK) cells have been proved to be an effective method of tumor immunotherapy in numerous preclinical and clinical studies. In our previous study, a new method was developed to prime and propagate CIK cells by the combination of IL-2 and IL-15, and this kind of CIK cells had enhanced antitumor effect on lung cancer. For renal cell carcinoma (RCC), immunotherapy plays an important role because of the poor efficacy of radiotherapy and chemotherapy. In this study, we further evaluated the antitumor effects of these enhanced CIK cells against RCC. Enhanced CIK cells were generated by IL-2 combined with IL-15 and identified by flow cytometry. HEK-293 and ACHN cell lines were used to verify the efficiency of CIK cells , and then the ACHN tumor xenograft model was also employed for study. In addition, the secreted cytokines including IFN-, granzyme B, TNF-, and perforin, as well as the local microstructure were also studied. Subsequently, 20 patients with RCC were enrolled into our study, and 11 patients were randomly divided into the autologous CIK treatment group for clinical research. The results showed that enhanced CIK cells exert better antitumor effects in RCC ( < 0.01 in HEK-293 and < 0.05 in ACHN)and ( < 0.05). Patients benefit overall survival from enhanced CIK therapy in our clinical study. Our present preclinical and clinical studies for the first time elucidated that these enhanced CIK cells would be used as an effective adjuvant therapy in the treatment of RCC.

摘要

细胞因子诱导的杀伤(CIK)细胞已被证明是许多临床前和临床研究中肿瘤免疫治疗的有效方法。在我们之前的研究中,开发了一种新方法,通过 IL-2 和 IL-15 的组合来启动和扩增 CIK 细胞,这种 CIK 细胞对肺癌具有增强的抗肿瘤作用。对于肾细胞癌(RCC),由于放化疗效果不佳,免疫疗法发挥着重要作用。在这项研究中,我们进一步评估了这些增强的 CIK 细胞对 RCC 的抗肿瘤作用。通过 IL-2 与 IL-15 联合产生增强的 CIK 细胞,并通过流式细胞术进行鉴定。使用 HEK-293 和 ACHN 细胞系验证 CIK 细胞的效率,然后还使用 ACHN 肿瘤异种移植模型进行研究。此外,还研究了包括 IFN-、颗粒酶 B、TNF-和穿孔素在内的分泌细胞因子以及局部微结构。随后,纳入 20 名 RCC 患者进行研究,其中 11 名患者随机分为自体 CIK 治疗组进行临床研究。结果表明,增强的 CIK 细胞在 RCC 中发挥更好的抗肿瘤作用(在 HEK-293 中 < 0.01,在 ACHN 中 < 0.05)和( < 0.05)。患者从我们的临床研究中的增强的 CIK 治疗中受益于总体生存。我们目前的临床前和临床研究首次阐明,这些增强的 CIK 细胞将作为治疗 RCC 的有效辅助治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/e95e16abf952/JHE2021-5709104.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/f54b9cf57498/JHE2021-5709104.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/a396f218d30f/JHE2021-5709104.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/b372e9a1ec4b/JHE2021-5709104.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/1cb23d09d3f2/JHE2021-5709104.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/bca1207d6a66/JHE2021-5709104.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/e95e16abf952/JHE2021-5709104.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/f54b9cf57498/JHE2021-5709104.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/a396f218d30f/JHE2021-5709104.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/b372e9a1ec4b/JHE2021-5709104.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/1cb23d09d3f2/JHE2021-5709104.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/bca1207d6a66/JHE2021-5709104.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8443387/e95e16abf952/JHE2021-5709104.006.jpg

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Increase in Efficacy of Checkpoint Inhibition by Cytokine-Induced-Killer Cells as a Combination Immunotherapy for Renal Cancer.细胞因子诱导的杀伤细胞作为联合免疫疗法增强对肾癌的疗效。
Int J Mol Sci. 2020 Apr 27;21(9):3078. doi: 10.3390/ijms21093078.
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A novel antibody-cell conjugation method to enhance and characterize cytokine-induced killer cells.
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Cytotherapy. 2020 Mar;22(3):135-143. doi: 10.1016/j.jcyt.2020.01.003.
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Combined induction with anti-PD-1 and anti-CTLA-4 antibodies provides synergistic antitumor effects in DC-CIK cells in renal carcinoma cell lines.抗PD-1和抗CTLA-4抗体联合诱导在肾癌细胞系的DC-CIK细胞中具有协同抗肿瘤作用。
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Improving Clinical Manufacturing of IL-15 Activated Cytokine-Induced Killer (CIK) Cells.提高白细胞介素 15 激活的细胞因子诱导的杀伤(CIK)细胞的临床生产。
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