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植物病毒和细菌纳米颗粒为癌症免疫治疗提供的TLR激活剂
Eunkyeong Jung1, Young Hun Chung2,3, Nicole F Steinmetz1,2,3,4,5,6
1Department of NanoEngineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, California 92093, United States.
Bioconjugate chemistry
|August 23, 2023
概括
病毒纳米颗粒有效地为癌症免疫疗法提供托尔类受体 (TLR) 激动剂,增强免疫细胞激活并减少瘤生长. 结合,而不是简单的混合,是改善抗瘤疗效和生存益处的关键.
科学领域:
- 免疫学 免疫学 免疫学
- 纳米技术纳米技术
- 在瘤学瘤学.
背景情况:
- 收费类受体 (TLRs) 对于免疫激活至关重要,也是有希望的癌症免疫治疗点.
- 小分子TLR激动剂由于副作用和药理动力学不佳而面临临临床限制.
- 基于病毒的纳米粒子提供了一个新的药物输送系统来克服这些挑战.
研究的目的:
- 研究病毒纳米颗粒 (VNP) 和病毒样颗粒 (VLP) 作为TLR激动剂药物递送系统的使用.
- 为了增强TLR激动剂的抗瘤功效和药理动力学特性.
- 评估结合与简单混合对治疗结果的影响.
主要方法:
- 结合TLR3或TLR7激动剂,对牛马赛克病毒 (CPMV) VNPs,牛胆斑病毒 (CCMV) VNPs和细菌菌 Qβ VLPs进行结合.
- 在体外评估免疫细胞激活和细胞因子的产生 (素6).
- 在体内评估小鼠模型中的瘤生长减少和存活率.
主要成果:
- 一个TLR7激动剂 (1V209) 与CPMV,CCMV和Qβ VLPs的结合强烈激活了免疫细胞并增加了互白素6的产生.
- 与自由激素或混合物相比,病毒颗粒结合的TLR7激动剂显著减少了小鼠的瘤生长和延长了小鼠的存活时间.
- 通过CPMV VNPs输送TLR3激动剂 (多I:C) 也提高了小鼠的存活率.
结论:
- 将TLR激动剂与VNP/VLP结合起来,对于增强抗瘤疗效至关重要.
- 简单地将激动剂与病毒颗粒混合并不能提供生存益处.
- VNPs/VLPs通过多价值呈现,延长瘤停留时间和免疫细胞向来提高TLR激动剂的疗效.
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