核酸适配子修饰的NK细胞外泌体对CD30阳性淋巴瘤细胞的靶向杀伤作用及其机制研究

批准号:
82000207
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
杨双汇
依托单位:
学科分类:
淋巴瘤与淋巴细胞疾病
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
杨双汇
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中文摘要
淋巴瘤是严重威胁人类健康的恶性血液肿瘤,因化疗缺乏特异性易致正常组织受损,精准治疗具有重要意义。CD30广泛表达于淋巴瘤细胞表面,是其重要的诊治靶点。核酸适配子以高度特异性及亲和力结合其靶点,且免疫原性低、易修饰、组织渗透性强。现有研究已报道一种可特异性结合CD30阳性淋巴瘤的核酸适配子。NK细胞外泌体可快速有效地杀伤肿瘤细胞,且较NK细胞有更强的杀伤潜力。但因其缺乏对肿瘤抗原的特异性识别,因此限制了其对肿瘤细胞的高效募集和杀伤效应。本课题前期实验探究了一种简单快捷将核酸适配子插入NK细胞膜的方法,并证明CD30核酸适配子修饰后的NK细胞对CD30阳性淋巴瘤的识别和杀伤力均增强。现将在细胞株、动物模型、临床样本中探究核酸适配子修饰的NK细胞外泌体对靶细胞的杀伤效应并探索其机制。本项目旨在探索简单快捷增强NK细胞外泌体对CD30淋巴瘤靶向杀伤效应的方法,进一步为恶性肿瘤的精准治疗提供新思路。
英文摘要
Lymphomas are hematological malignancies that greatly threaten human health, for chemotherapies lack specificity which can easily harm normal tissues, precision therapy is of great significance. CD30 is widely expressed on membrane of lymphoma cells, and acts as important target for both diagnosis and treatments of lymphoma. Aptamers can bind to their targets with high specificity and affinity, and has low immunogenecity, good capacity for modification and excellent tissue permeability. Existing study has reported an aptamer that can bind CD30 positive lymphoma cells with high specificity. NK cell exosomes can quickly kill tumor cells, and has higher potential for killing tumor cells. But the lack for specific recognition of tumor antigen restricted efficient recruitment and killing effects towards tumor cells. Our pre-experimental data explored a simple and quick method to insert aptamer to NK cell membrane, and proved that CD30 aptamer modified NK cell has enhanced recognition and killing effects to CD30 positive lymphoma. Now we will explore the killing efficiency of CD30 aptamer modified NK cell exosomes in target cells and explore the mechanism in cell lines, animal models and clinical samples. Our project aim to explore a simple and quick method that can enhance specific killing effects of NK cell exosomes toward CD30 lymphoma cells, and further provide new insights for precision therapy of malignancies.
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