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抗体展示的细胞外囊泡用于靶向癌症治疗。

Antibody-displaying extracellular vesicles for targeted cancer therapy.

机构信息

Department of Laboratory Medicine, Unit for Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.

Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Nat Biomed Eng. 2024 Nov;8(11):1453-1468. doi: 10.1038/s41551-024-01214-6. Epub 2024 May 20.

DOI:10.1038/s41551-024-01214-6
PMID:38769158
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11584392/
Abstract

Extracellular vesicles (EVs) function as natural delivery vectors and mediators of biological signals across tissues. Here, by leveraging these functionalities, we show that EVs decorated with an antibody-binding moiety specific for the fragment crystallizable (Fc) domain can be used as a modular delivery system for targeted cancer therapy. The Fc-EVs can be decorated with different types of immunoglobulin G antibody and thus be targeted to virtually any tissue of interest. Following optimization of the engineered EVs by screening Fc-binding and EV-sorting moieties, we show the targeting of EVs to cancer cells displaying the human epidermal receptor 2 or the programmed-death ligand 1, as well as lower tumour burden and extended survival of mice with subcutaneous melanoma tumours when systemically injected with EVs displaying an antibody for the programmed-death ligand 1 and loaded with the chemotherapeutic doxorubicin. EVs with Fc-binding domains may be adapted to display other Fc-fused proteins, bispecific antibodies and antibody-drug conjugates.

摘要

细胞外囊泡 (EVs) 作为天然的递药载体和生物信号在组织间传递的介质发挥功能。在这里，通过利用这些功能，我们表明，用针对片段可结晶 (Fc) 结构域的抗体结合部分修饰的 EVs 可以用作靶向癌症治疗的模块化递药系统。Fc-EVs 可以用不同类型的免疫球蛋白 G 抗体进行修饰，从而靶向几乎任何感兴趣的组织。通过筛选 Fc 结合和 EV 分选部分对工程化 EV 进行优化后，我们表明，EV 可以靶向显示人表皮受体 2 或程序性死亡配体 1 的癌细胞，并且当用装载有化疗药物阿霉素的针对程序性死亡配体 1 的抗体修饰并系统注射时，具有皮下黑色素瘤肿瘤的小鼠的肿瘤负担降低和存活时间延长。具有 Fc 结合结构域的 EV 可适应显示其他 Fc 融合蛋白、双特异性抗体和抗体药物偶联物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/69a6e5a798d2/41551_2024_1214_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/45104692c4bb/41551_2024_1214_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/029271437e7b/41551_2024_1214_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/1c479fcaf1ba/41551_2024_1214_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/aa69a6d5a8f1/41551_2024_1214_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/69a6e5a798d2/41551_2024_1214_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/45104692c4bb/41551_2024_1214_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/2ad9a6f2b27c/41551_2024_1214_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/649d145744a5/41551_2024_1214_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/029271437e7b/41551_2024_1214_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/1c479fcaf1ba/41551_2024_1214_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/aa69a6d5a8f1/41551_2024_1214_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a36/11584392/69a6e5a798d2/41551_2024_1214_Fig7_HTML.jpg

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