Antitumor Activity of Lipid-DNA Aptamer Modified T Lymphocytes in Carcinoma.
Antitumor Activity of Lipid-DNA Aptamer Modified T Lymphocytes in Carcinoma.
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DOI：
10.1166/jbn.2020.2954
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发表时间：
2020-07
影响因子：
2.9
通讯作者：
Liping Zhong;L. Gan;Zhiming Deng;Xiuli Liu;Hongmei Peng;Hongliang Tang;Xueling Liu;Fang Fang-Fang;Fei Yao;Wanqiu Li;Zhenbo Liu;Weijia Hou;Cheng Cui;Yongxiang Zhao;W. Tan;Wei Shi;Jian He
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文献类型：
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作者：
Liping Zhong;L. Gan;Zhiming Deng;Xiuli Liu;Hongmei Peng;Hongliang Tang;Xueling Liu;Fang Fang-Fang;Fei Yao;Wanqiu Li;Zhenbo Liu;Weijia Hou;Cheng Cui;Yongxiang Zhao;W. Tan;Wei Shi;Jian He
胰腺导管腺癌（PDAC）是一种致命疾病，目前尚无有效的治疗方法。 PDAC免疫治疗疗效低的主要原因之一是CD8+ T细胞浸润有限，且PDAC中不存在新抗原。适体代表单链寡核苷酸，能够以高特异性结合特定靶标。我们开发了DNA缀合物并制备了二酰基磷脂适配体XQ-2d，其具有用于PDAC的靶向治疗和诊断的潜力。在本研究中，采用流式细胞术和荧光显微镜来评估Lipo-XQ-2d探针是否可以锚定在活化的T细胞上以构成特异性识别PDAC PL45细胞的配体。采用流式细胞术测定活化 T 细胞的细胞毒性。结果显示Lipo-XQ-2d探针可以插入T细胞中，并且与T细胞和PL45细胞特异性结合。此外，Lipo-XQ-2d探针可以在体外重定向T细胞杀死PL45细胞，并且对细胞没有毒性。总之，脂质DNA适配体修饰的T淋巴细胞可能在体外有效杀死PDAC，支持T细胞过继免疫治疗的临床应用。
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with no current effective therapeutics. One of the main reasons for the low efficacy of PDAC immunotherapy is the limited CD8+ T cell infiltration, without neo antigen present in PDAC. Aptamers represent single-stranded oligonucleotides which bind to specific targets with high specificity. We developed DNA conjugates and prepared diacyl phospholipid-aptamer XQ-2d which has potential for the targeted therapy and diagnosis of PDAC. In this study, flow cytometry and fluorescence microscopy were employed to assess whether the Lipo-XQ-2d probe could anchor on activated T cells to constitute ligands specifically recognizing PDAC PL45 cells. Flow cytometry was employed to determine cytotoxicity in activated T cells. Results showed that the Lipo-XQ-2d probe could be inserted into T cells, and was specifically bound to both T cells and PL45 cells. In addition, the Lipo-XQ-2d probe redirected T cells to kill PL45 cells in vitro and was not toxic to cells. In conclusion, lipid-DNA-aptamer-modified T-lymphocytes might effectively kill PDAC in vitro, supporting the clinical application of T cell adoptive immunotherapy.