决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Exosomes as a Therapeutic Strategy in Cancer: Potential Roles as Drug Carriers and Immune Modulators.
基于外泌体的肿瘤免疫治疗正围绕人工激活免疫系统以对抗肿瘤这一理念快速推进。
基于外泌体的癌症免疫治疗发展迅速,其理念是人为激活免疫系统以对抗癌症。外泌体具有天然生物活性、低毒性和免疫原性,可从机制上改变肿瘤微环境、增强免疫应答,并作为高效药物递送载体。若要增加临床应用,需要准确识别外泌体在肿瘤环境中的作用机制,并优化其分离、纯化和表征方法。可在供体细胞分离前后通过载荷装载或表面修饰改造外泌体,以增强治疗应用价值。这些工程化外泌体可直接靶向肿瘤部位的癌细胞,也可间接激活肿瘤微环境中的先天免疫和适应性免疫应答。若与疫苗、免疫检查点疗法和CAR-T细胞等传统癌症免疫治疗技术联合,效果尤其显著。此类方法可改善抗肿瘤应答、诱导长期免疫,并解决传统疗法在实体瘤中穿透性差及肿瘤微环境免疫抑制等局限。本综述旨在全面、详细概述工程化外泌体作为药物递送系统的直接作用,以及其通过免疫调节间接抗癌的效应。此外,文章还将讨论新型免疫治疗选择。
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.
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