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One‐Step Method for Instant Generation of Advanced Allogeneic NK Cells
Advanced Science ( IF 15.1 ) Pub Date : 2018-09-27 , DOI: 10.1002/advs.201800447
Daniel Y Lee 1, 2 , Kwang Suk Lim 1, 3 , Gabriel M Valencia 1 , Minjin Jung 2 , David A Bull 1, 2 , Young-Wook Won 1, 2
Affiliation  

Conventional combinatorial anticancer therapy has shown promising outcomes; still, a significant interest in developing new methods to reinforce and possibly merge chemotherapy and immunotherapy persists. Here, a new one‐step method that immediately modifies immune cells into a targeted form of chemoimmunotherapy through spontaneous and rapid incorporation of hydrophobized antibody–drug conjugates (ADCs) on the surface of immune cells is presented. Therapeutic objectives of this approach include targeted delivery of a potent chemotherapeutic agent to avoid adverse effects, enhancing the mobilization of infused immune cells toward tumor sites, and preserving the intense cytotoxic activities of immune cells against tumor cells. The embedding of hydrophobized ADCs on the immune cell membrane using the strategy in this study provides noninvasive, nontoxic, and homogenous modifications that transiently arm immune cells with highly potent cytotoxic drugs targeted toward cancer cells. The resulting surface‐engineered immune cells with ADCs significantly suppress the tumor growth and drive the eradication of target cancer cells through combinatorial anticancer effects. This novel strategy allows convenient and timely preparation of advanced chemoimmunotherapy on a single immune cell to treat various types of cancer.

中文翻译:

即时生成先进同种异体 NK 细胞的一步法

传统的联合抗癌疗法已显示出有希望的结果;尽管如此,人们仍然对开发新方法来加强和可能合并化疗和免疫疗法抱有浓厚的兴趣。在这里,提出了一种新的一步法,通过在免疫细胞表面自发、快速地掺入疏水化抗体药物偶联物(ADC),立即将免疫细胞修饰为化学免疫疗法的靶向形式。这种方法的治疗目标包括有针对性地递送有效的化疗剂以避免副作用,增强输注的免疫细胞向肿瘤部位的动员,以及保留免疫细胞针对肿瘤细胞的强烈细胞毒活性。使用本研究中的策略将疏水化 ADC 嵌入免疫细胞膜上,提供了非侵入性、无毒且同质的修饰,可以瞬间用针对癌细胞的高效细胞毒性药物武装免疫细胞。由此产生的带有 ADC 的表面工程免疫细胞可显着抑制肿瘤生长,并通过组合抗癌作用推动目标癌细胞的根除。这种新颖的策略可以方便、及时地在单个免疫细胞上准备先进的化学免疫疗法来治疗各种类型的癌症。
更新日期:2018-09-27
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