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:Current and future perspectives on CAR-T cell therapy for renal cell carcinoma: A comprehensive review.
在肾细胞癌(RCC)的临床环境中,诸如肿瘤特异性T细胞反应等免疫反应可以是自发事件,也可以由检查点抑制剂、细胞因子和其他免疫治疗方式引发。
在肾细胞癌(RCC)的临床环境中,诸如肿瘤特异性T细胞反应等免疫反应可以是自发事件,也可以由检查点抑制剂、细胞因子和其他免疫治疗方式引发。免疫治疗的结果已在治疗方法和患者预后方面带来了显著进步。nivolumab主要作为二线单药治疗的获批,以及新型联合疗法作为一线治疗的最新获批,确立了免疫治疗在RCC治疗中的重要意义。在这一视角下,嵌合抗原受体(CAR)-T细胞疗法代表了免疫治疗发展领域的一项重大进展。这种治疗方式使T细胞能够在细胞表面表达特异性CAR,并将其回输给患者以治疗相应的肿瘤细胞。在血液系统恶性肿瘤中显示出治疗潜力后,这种新的治疗方法已成为实体肿瘤治疗方式的强有力候选。尽管与既往T细胞调节免疫疗法相比,CAR-T细胞疗法已显示出前景和临床获益,但仍需进一步研究以克服不利的生理环境以及诸如缺乏特异性分子靶点、CAR-T细胞耗竭、敌对的肿瘤微环境和on/off-tumor毒性等障碍。目前正在考虑多种方法,研究也在持续进行以克服这些问题。在这篇综合性综述中,我们提供CAR-T细胞疗法在RCC中的理论基础和初步结果,并讨论新兴的新策略和未来方向。
In the clinical setting of renal cell carcinoma (RCC), immune reactions such as tumor-specific T cell responses can be spontaneous events or can be elicited by checkpoint inhibitors, cytokines, and other immunotherapy modalities. The results from immunotherapy have led to significant advances in treatment methods and patient outcomes. The approval of nivolumab primarily as a second-line monotherapy and the latest approval of novel combination therapies as first-line treatment have established the significance of immunotherapy in the treatment of RCC. In this perspective, chimeric antigen receptor (CAR)-T cell therapy represents a major advance in the developing field of immunotherapy. This treatment modality facilitates T cells to express specific CARs on the cell surface which are reinfused to the patient to treat the analogous tumor cells. After showing treatment potential in hematological malignancies, this new therapeutic approach has become a strong candidate as a therapeutic modality for solid neoplasms. Although CAR-T cell therapy has shown promise and clinical benefit compared to previous T-cell modulated immunotherapies, further studies are warranted to overcome unfavorable physiological settings and hindrances such as the lack of specific molecular targets, depletion of CAR-T cells, a hostile tumor microenvironment, and on/off-tumor toxicities. Several approaches are being considered and research is ongoing to overcome these problems. In this comprehensive review, we provide the rationale and preliminary results of CAR-T cell therapy in RCC and discuss emerging novel strategies and future directions.
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