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 in review: A new frontier in CAR-T cell therapies.
Exosomes in review: A new frontier in CAR-T cell therapies.
外泌体是细胞外囊泡,通过运输关键蛋白质和遗传物质促进细胞间通讯。
外泌体是通过运输关键蛋白质和遗传物质来促进细胞间通讯的细胞外载体。每个外泌体本质上都反映其来源细胞,甚至能够模拟亲代细胞的效应功能。近年来,随着 CAR-T 疗法的成功,表征源自 CAR-T 细胞的外泌体引起了越来越多的兴趣。CAR 外泌体含有与其亲代细胞相同的细胞毒性颗粒,并在体外和动物模型中显示出显著的抗肿瘤活性。此外,在动物模型中输注 CAR 外泌体未产生细胞因子释放综合征。相反,也有新型双特异性抗体靶向肿瘤来源的外泌体,以期破坏由恶性细胞产生的外泌体所介导的免疫抑制通路。两个最有前景的例子包括 (a) BsE CD73 x EpCAM,其结合并抑制外泌体 CD73 以抑制免疫抑制性腺苷的产生,以及 (b) BsE CD3 x PD-L1,其靶向肿瘤微环境内的外泌体 PD-L1,以引导细胞毒性 T 细胞朝向肿瘤细胞。随着我们对外泌体生物学的理解不断发展,细胞疗法进步的机会也将随之增长。
Exosomes are extracellular vehicles that facilitate intra-cellular communication via transport of critical proteins and genetic material. Every exosome is intrinsically reflective of the cell from which it was derived and can even mimic effector functions of their parent cells. In recent years, with the success of CAR-T therapies, there has been growing interest in characterizing exosomes derived from CAR-T cells. CAR exosomes contain the same cytotoxic granules as their parent cells and have demonstrated significant anti-tumor activity in vitro and in animal models. Moreover, infusion of CAR exosomes in animal models did not generate cytokine release syndrome. Conversely, there are also novel bispecific antibodies which target tumor-derived exosomes in hopes of derailing immunosuppressive pathways mediated by exosomes produced from malignant cells. The two most promising examples include (a) BsE CD73 x EpCAM which binds and inhibits exosomal CD73 to suppress production of immunosuppressant adenosine and (b) BsE CD3 x PD-L1 which targets exosomal PD-L1 within the tumor microenvironment to guide cytotoxic T-cells towards tumor cells. As our understanding of exosome biology continues to evolve, opportunities for advances in cellular therapies will grow in tandem.
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