Abedi Azam, Moosazadeh Moghaddam Mehrdad, Kachuei Reza, Imani Fooladi Abbas Ali
Tissue Engineering and Regenerative Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Molecular Biology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Biochim Biophys Acta Rev Cancer. 2025 Feb;1880(1):189238. doi: 10.1016/j.bbcan.2024.189238. Epub 2024 Dec 16.
Exosome-based cancer immunotherapy is advancing quickly on the concept of artificially activating the immune system to combat cancer. They can mechanistically change the tumor microenvironment, increase immune responses, and function as efficient drug delivery vehicles because of their inherent bioactivity, low toxicity, and immunogenicity. Accurate identification of the mechanisms of action of exosomes in tumor environments, along with optimization of their isolation, purification, and characterization methods, is necessary to increase clinical applications. Exosomes can be modified through cargo loading and surface modification to enhance their therapeutic applications, either before or after the donor cells' isolation. These engineered exosomes can directly target tumor cells at the tumor site or indirectly activate innate and adaptive immune responses in the tumor microenvironment. This approach is particularly effective when combined with traditional cancer immunotherapy techniques such as vaccines, immune checkpoints, and CAR-T cells. It can improve anti-tumor responses, induce long-term immunity, and address the limitations of traditional therapies, such as poor penetration in solid tumors and immunosuppressive environments. This review aims to provide a comprehensive and detailed overview of the direct role of engineered exosomes as drug delivery systems and their immunomodulatory effects on tumors as an indirect approach to fighting cancer. Additionally, it will discuss novel immunotherapy options.
基于外泌体的癌症免疫疗法正基于人工激活免疫系统来对抗癌症的理念迅速发展。由于其固有的生物活性、低毒性和免疫原性,它们可以通过机制改变肿瘤微环境、增强免疫反应,并作为高效的药物递送载体发挥作用。准确识别外泌体在肿瘤环境中的作用机制,以及优化其分离、纯化和表征方法,对于增加临床应用是必要的。外泌体可以通过装载货物和表面修饰进行改造,以增强其治疗应用,无论是在供体细胞分离之前还是之后。这些工程化外泌体可以直接靶向肿瘤部位的肿瘤细胞,或间接激活肿瘤微环境中的先天和适应性免疫反应。当与传统癌症免疫疗法技术(如疫苗、免疫检查点和嵌合抗原受体T细胞)联合使用时,这种方法特别有效。它可以改善抗肿瘤反应,诱导长期免疫,并解决传统疗法的局限性,如在实体瘤和免疫抑制环境中的穿透性差。本综述旨在全面详细地概述工程化外泌体作为药物递送系统的直接作用及其作为对抗癌症的间接方法对肿瘤的免疫调节作用。此外,还将讨论新型免疫疗法选项。