多面性纳米药物增强金属免疫疗法用于肝细胞癌
Yongwei Hu1, Kaiming He2, Mingshen Zhang2
1Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Organ Transplantation Institute of Sun Yat-sen University, Organ Transplantation Research Center of Guangdong Province, Guangdong Province Engineering Laboratory for Transplantation Medicine, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China; Laboratory of Biomaterials and Translational Medicine Center for Nanomedicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
这项研究结合了伦瓦替尼和Cobalt (Co2+) 来克服肝细胞癌 (HCC) 中的免疫疗法耐药性. 新型纳米集群疗法增强T细胞活性,减少瘤生长,为无法切除的HCC提供了有前途的治疗方法.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 纳米医学是一种纳米医学.
背景情况:
- 肝细胞癌 (HCC) 因其免疫抑制性瘤微环境而构成重大治疗挑战.
- 目前的免疫疗法,包括免疫检查点抑制剂 (ICI),在HCC中表现出有限的疗效,通常是由于T细胞透不良和瘤血管系统异常.
研究的目的:
- 研究一种新的治疗策略,将伦瓦替尼和 (Co2+) 结合起来,以增强抗瘤免疫力,克服HCC的免疫疗法耐药性.
- 开发和评估pH调节的自组装纳米集群 (Co+Len@OVA) 以提供有针对性和协同治疗效果.
主要方法:
- 机理学研究阐明了伦瓦替尼抑制PD-L1翻译和Co2+诱导ROS依赖DNA损伤和cGAS-STING通路激活.
- 开发Co+Len@OVA纳米集群用于瘤选择性积累和血管正常化.
- 在小鼠HCC模型中对组合疗法 (Co+Len@OVA与抗PD1) 的评估.
主要成果:
- Co+Len@OVA纳米集群促进了抗PD1抗体透到瘤中,并使瘤血管正常化.
- 结合疗法显著减少了与单一疗法相比,小鼠HCC模型中的瘤体积.
- 该疗法通过增强树突细胞成熟,增加CD8+ T细胞和减少调节性T细胞 (Tregs) 来重塑瘤微环境.
结论:
- 将金属免疫疗法与血管调节相结合的组合方法为治疗不可切除的HCC提供了有效的策略.
- 这种策略有效地克服了免疫抑制性瘤微环境,并提高了抗PD1免疫疗法的疗效.
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