来自骨髓细胞的抑制细胞向的类似病毒的颗粒协同激活癌症免疫治疗的先天免疫反应
Zhixiong Zhu1, Shuqin Cao2, Hanwen Li2
1State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
概括
这项研究开发了新的类似病毒的颗粒 (VLPs),向髓质衍生抑制细胞 (MDSCs),以增强癌症免疫疗法. 这些工程VLP重新编程瘤微环境,并显示出对转移的有效性,并与PD-1阻断结合.
科学领域:
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
- 在瘤学瘤学.
背景情况:
- 瘤微环境 (TME) 极大地影响了癌症的进展.
- 向与瘤相关的巨细胞和髓质衍生抑制细胞 (MDSCs) 等免疫细胞是癌症免疫疗法的关键策略.
- 病毒样粒子 (VLP) 为癌症治疗中向药物输送提供了一个多功能平台.
研究的目的:
- 为癌症免疫疗法设计由牛菌菌斑病毒 (CCMV) 衍生的VLP,封装氧化dSDNA (CPD VLP).
- 增强瘤向特异性并通过将MDSC向酸与CPD VLPs相结合来降低毒性,从而创建CPD-TP VLPs.
- 评估CPD-TP VLPs在临床前癌症模型中的抗瘤疗效,包括转移和组合疗法.
主要方法:
- 在CCMV中封装氧化dDNA,以形成CPDVLP.
- 将MDSC向的合到CPD VLPs中以创建CPD-TP VLPs.
- 在小鼠模型中评估巨细胞吸收VLP,诱导免疫通路 (cGAS-STING,NLRP3炎症体) 和抗瘤反应.
主要成果:
- CPD VLPs被巨细胞有效地吸收,激活了cGAS-STING和NLRP3依赖性热灭菌途径.
- 通过重编程TME,CPD-TP VLPs表现出瘤定位能力,并诱导显著的抗瘤反应.
- 在"免疫感冒"模型中,CPD-TP VLPs显示对乳腺癌肺转移的有效性,并与PD-1阻断结合改善了反应.
结论:
- 工程VLPs (CPD-TP VLPs) 通过调节TME和准MDSCs,代表了癌症免疫疗法的有希望的策略.
- 这种基于VLP的方法为治疗转移性癌症和克服对PD-1阻断等现有免疫疗法的耐药性提供了潜力.
- 该研究提出了一种新的VLP设计,用于下一代癌症疫苗,具有增强的向性和治疗潜力.
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