聚合物微贴片作为用于瘤治疗的天然杀手细胞参与者
Supriya Prakash1,2, Ninad Kumbhojkar1,2, Andrew Lu1
1Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, Massachusetts 02134, United States.
ACS nano
|August 11, 2023
概括
聚合物微贴片,称为微颗粒作为细胞参与剂 (MACE),有效地激活自然杀手 (NK) 细胞. 这种基于材料的方法增强了NK细胞的持久性和抗瘤活性,为癌症免疫治疗提供了一个有前途的策略.
科学领域:
- 生物材料科学 生物材料科学
- 免疫学 免疫学 免疫学
- 癌症治疗 癌症治疗
背景情况:
- 天然杀手 (NK) 细胞疗法在癌症治疗方面表现有前途,但因体内持久性和 anergy 缺乏而受到阻碍.
- 现有的增强NK细胞功能的方法,如基因修饰或细胞因子支持,面临由于瘤微环境和非目标效应的局限性.
研究的目的:
- 开发一种基于材料的策略,以持续和有针对性地激活NK细胞.
- 调查聚合物微贴片的有效性,称为微粒作为细胞参与剂 (MACE),作为增强NK细胞基础癌症免疫治疗的新平台.
主要方法:
- 用NK细胞受体向抗体进行表面修饰的聚乳糖合糖酸 (PLGA) 微贴片 (4-8μm) 的制造.
- 评估MACE粘附,NK细胞激活,活力,穿越内皮细胞的迁移,以及与其他免疫细胞的*体外*交叉交谈.
- 在小鼠黑色素瘤肺转移模型中评估NK-MACE的*in vivo*抗瘤疗效.
主要成果:
- MACE对NK细胞表现出强大的粘附性,在没有外源性细胞因子的情况下诱导强大的激活,超过了基于纳米粒子的激活.
- 结合MACE的NK细胞保持了活力,表现出跨内皮迁移,并显示出*体外*的抗瘤活性和免疫细胞激活.
- 与未经修改的NK细胞相比,在临床前的肺转移模型中,NK-MACE的采用转移显著改善了抗瘤疗效.
结论:
- 作为细胞参与剂的微粒子 (MACE) 为持续的NK细胞激活提供了一个可扩展和有效的基于材料的平台.
- MACE代表了一种有希望的策略,可以克服NK细胞的局限性,并提高NK细胞的癌症免疫疗法的疗效.
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