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:Immunotherapeutic Strategies in Chronic Lymphocytic Leukemia: Advances and Challenges.
基于免疫的治疗策略彻底改变了血液系统疾病的格局,因为它们引入了增强针对肿瘤细胞的免疫反应这一概念。
免疫治疗策略显著改变了血液系统疾病的治疗格局,其核心理念是增强针对肿瘤细胞的免疫应答。抗CD20单克隆抗体最早成功用于慢性淋巴细胞白血病(CLL)化学免疫治疗方案。此后,研究者在CLL中研究了多种免疫治疗方法,旨在利用或诱导针对白血病细胞的抗肿瘤免疫应答。遗憾的是,尽管初步数据令人鼓舞,早期临床研究结果在疾病控制方面并不理想,尤其是免疫疗法单独使用时;主要原因是CLL相关免疫功能障碍阻碍了有效抗肿瘤应答。随着对免疫细胞与肿瘤细胞复杂相互作用的认识加深,研究者开发出依赖新型药物与免疫疗法协同作用的联合治疗策略。本文概述CLL中较成功且有前景的免疫疗法,包括基于抗体的治疗(如单克隆抗体、双特异性抗体、双特异性或三特异性杀伤细胞衔接器)和过继细胞疗法(如CAR T细胞和NK细胞),并介绍成功的新型联合策略及未来展望。
Immune-based therapeutic strategies have drastically changed the landscape of hematological disorders, as they have introduced the concept of boosting immune responses against tumor cells. Anti-CD20 monoclonal antibodies have been the first form of immunotherapy successfully applied in the treatment of CLL, in the context of chemoimmunotherapy regimens. Since then, several immunotherapeutic approaches have been studied in CLL settings, with the aim of exploiting or eliciting anti-tumor immune responses against leukemia cells. Unfortunately, despite initial promising data, results from pilot clinical studies have not shown optimal results in terms of disease control - especially when immunotherapy was used individually - largely due to CLL-related immune dysfunctions hampering the achievement of effective anti-tumor responses. The growing understanding of the complex interactions between immune cells and the tumor cells has paved the way for the development of new combined approaches that rely on the synergism between novel agents and immunotherapy. In this review, we provide an overview of the most successful and promising immunotherapeutic modalities in CLL, including both antibody-based therapy (i.e. monoclonal antibodies, bispecific antibodies, bi- or tri- specific killer engagers) and adoptive cellular therapy (i.e. CAR T cells and NK cells). We also provide examples of successful new combination strategies and some insights on future perspectives.
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