聚焦素基纳米疫苗与瘤相关的巨细胞向和抗PD-1免疫疗法对抗固体瘤具有协同作用
Ana I Matos1,2, Carina Peres1,2, Barbara Carreira1
1Grouf of BioNanoSciences - Drug Delivery and Immunoengineering, Research Institute for Medicines (iMed.ULisboa), Department of Pharmacy, Pharmacology and Health Technologies, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, 1649-003, Portugal.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|July 11, 2023
概括
这项研究引入了一种新的纳米疫苗策略,将抗原输送与免疫检查点封锁相结合. 这种方法增强了抗瘤免疫力,控制了瘤生长,为改善癌症免疫治疗提供了潜力.
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:
- 免疫检查点封锁有希望,但对许多癌症患者的长期疗效有限.
- 与瘤相关的巨细胞 (TAM) 和转化生长因子-β (TGF-β) 促进免疫抑制性瘤微环境 (TME).
研究的目的:
- 研究一种用于癌症免疫治疗的新型聚焦沙 (POx) - 聚糖乳糖酸 (PLGA) 纳米疫苗策略.
- 评估纳米疫苗与TAM调节和PD-1阻断的组合,以增强抗瘤反应.
主要方法:
- 开发POx-Mannose (Man) 纳米疫苗,同时提供抗原,辅助剂和TGF-β调节剂.
- 组合疗法包括POx-Man纳米疫苗,pexidartinib (一个TAM调节器) 和抗PD-1阻塞.
- 在MC38,CT26和B16F10小鼠癌症模型中评估抗瘤功效.
主要成果:
- POx-Man纳米疫苗诱导了强大的抗原特异性CD8+T细胞反应,比PEG-Man纳米疫苗更有效地控制瘤生长.
- 在多种癌症模型中,POx-Man纳米疫苗与pexidartinib和PD-1阻断的组合协同抑制了瘤生长并改善了生存率.
- 这种组合策略即使在免疫性较差的B16F10黑色素瘤模型中也表现出有效性.
结论:
- 开发的纳米疫苗,当与TAM抑制和PD-1阻断相结合时,代表了克服免疫疗法耐药性的有希望的策略.
- 这种多方位的方法具有显著的潜力,可以改善固体瘤患者的临床结果.
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