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用于癌症免疫治疗的基因可编程融合细胞囊泡
作者:小柯机器人 发布时间:2021/10/21 16:15:56

新加坡国立大学Xiaoyuan Chen团队报道了基因可编程融合细胞囊泡用于癌症免疫治疗。相关研究成果发表在2021年10月18日出版的国际知名学术期刊《德国应用化学》。

高效激活宿主对癌症的免疫已经成为一种很有前途的治疗策略。然而,癌细胞通过先天性和适应性免疫效应物抵抗宿主免疫反应。尤其是,肿瘤细胞上的CD47通过与SIRPα相互作用保护它们免受巨噬细胞吞噬,而PD-L1与其受体PD-1相互作用并抑制T细胞介导的肿瘤杀伤。

该文中,研究人员报告显示高亲和力SIRPα变异体和PD-1的遗传可编程融合细胞囊泡(Fus CV)可以禁用这两种机制。Fus-CVs双重阻断CD47和PD-L1可显著增加巨噬细胞对癌细胞的吞噬作用,促进抗原提呈,并激活抗肿瘤T细胞免疫。此外,Fus-CVs的双特异性靶向设计确保了对肿瘤细胞的更好靶向性,但对其他细胞的靶向性较小,从而减少了系统性副作用并提高了治疗效果。在恶性黑色素瘤和乳腺癌模型中,研究人员证明Fus CVs通过抑制术后肿瘤复发和转移显著提高模型动物的总体生存率。Fus-CVs适合于通过基因工程蛋白质展示。以上优势,加上从源细胞继承的其他独特特性,使Fus-CVs成为多靶向免疫检查点阻断治疗的一个有吸引力的平台。

附:英文原文

Title: Genetically Programmable Fusion Cellular Vesicles for Cancer Immunotherapy

Author: Qian-Fang Meng, Yuyue Zhao, Chunbo Dong, Lujie Liu, Yuanwei Pan, Jialin Lai, Zhida Liu, Guang-Tao Yu, Xiaoyuan Chen, Lang Rao

Issue&Volume: 2021-10-18

Abstract: Effectively activating host immunity against cancer has already become a promising therapeutic strategy. However, cancer cells resist to the host immune response through both innate and adaptive immune effectors. Especially, CD47 on tumor cells protects them from macrophage phagocytosis through interaction with SIRPα, while PD-L1 interacts with its receptor PD-1 and dampens T cell-mediated tumor killing. Herein, we report that genetically programmable fusion cellular vesicles (Fus-CVs) displaying high-affinity SIRPα variants and PD-1 can disable both mechanisms. Dual-blockade of CD47 and PD-L1 with Fus-CVs significantly increases the phagocytosis of cancer cells by macrophages, promotes antigen presentation, and activates antitumor T-cell immunity. Moreover, the bispecific targeting design of Fus-CVs ensures better targeting on tumor cells, but less on other cells, which reduces systemic side effects and enhances therapeutic efficacies. In malignant melanoma and mammary carcinoma models, we demonstrate that Fus-CVs significantly improve overall survival of model animals by inhibiting post-surgery tumor recurrence and metastasis. The Fus-CVs are suitable for protein display by genetic engineering. These advantages, integrated with other unique properties inherited from source cells, make Fus-CVs an attractive platform for multi-targeting immune checkpoint blockade therapy.

DOI: 10.1002/anie.202108342

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202108342

期刊信息

Angewandte Chemie:《德国应用化学》,创刊于1887年。隶属于德国化学会,最新IF:12.959
官方网址:https://onlinelibrary.wiley.com/journal/15213773
投稿链接:https://www.editorialmanager.com/anie/default.aspx