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:The Hematology of Tomorrow Is Here-Preclinical Models Are Not: Cell Therapy for Hematological Malignancies.
本综述的目的是介绍关于几种形式的细胞疗法在血液系统恶性肿瘤中的临床应用以及可用于其研究的临床前模型的当前知识。
本综述的目的是介绍目前关于几种形式细胞疗法在血液系统恶性肿瘤中的临床应用知识,以及可用于其研究的临床前模型。在同种异体造血干细胞移植的背景下,间充质基质细胞被用于帮助干细胞植入和扩增,并控制移植物抗宿主病。我们进一步总结了有前景的细胞免疫治疗形式的现状,包括旨在根除白血病起源细胞即白血病干细胞的 CAR T 细胞和 CAR NK 细胞疗法。其他形式细胞免疫治疗的更新,如 NK 细胞、CIK 细胞和 CAR CIK 细胞,在 AML 中显示出令人鼓舞的结果。讨论了可用于疾病建模和治疗疗效预测的体内模型的考量,特别关注其在研究健康和疾病状态下造血干细胞重建、移植物抗宿主病和免疫治疗方面的优势和劣势。尽管目前存在局限性,细胞治疗是一个快速发展的领域,有望在不久的将来提高治愈率。因此,我们可能正在见证未来血液学的诞生。为了进一步支持其发展,迫切需要改进的临床前模型,包括小鼠中的人源化微环境。
The purpose of this review is to present the current knowledge on the clinical use of several forms of cell therapy in hematological malignancies and the preclinical models available for their study. In the context of allogeneic hematopoietic stem cell transplants, mesenchymal stromal cells are pursued to help stem cell engraftment and expansion, and control graft versus host disease. We further summarize the status of promising forms of cellular immunotherapy including CAR T cell and CAR NK cell therapy aimed at eradicating the cells of origin of leukemia, i.e., leukemia stem cells. Updates on other forms of cellular immunotherapy, such as NK cells, CIK cells and CAR CIK cells, show encouraging results in AML. The considerations in available in vivo models for disease modelling and treatment efficacy prediction are discussed, with a particular focus on their strengths and weaknesses for the study of healthy and diseased hematopoietic stem cell reconstitution, graft versus host disease and immunotherapy. Despite current limitations, cell therapy is a rapidly evolving field that holds the promise of improved cure rates, soon. As a result, we may be witnessing the birth of the hematology of tomorrow. To further support its development, improved preclinical models including humanized microenvironments in mice are urgently needed.
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