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:A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?
近年来,随着嵌合抗原受体(CAR)T 细胞疗法在血液系统肿瘤中取得突破性进展,以及细胞工程技术的进步,对其他免疫细胞的探索受到了广泛关注。
近年来,嵌合抗原受体(CAR)T 细胞治疗在血液系统癌症中取得突破,细胞工程技术也不断进步,促使研究者广泛探索其他免疫细胞。CAR 疗法已从 T 细胞拓展至 CAR 自然杀伤(NK)细胞和 CAR 巨噬细胞,这些疗法已在临床试验领域占据重要位置。CAR 黏膜相关恒定 T(MAIT)细胞等较少见的免疫细胞也开始受到关注。这一进展正在推动精准医疗,并促进现成型生物疗法的开发。鉴于 NK 细胞的独特特性,过继性 NK 细胞免疫治疗已发展为通用、异体、“现成型”治疗策略。CAR-NK 细胞具有靶向肿瘤的特异性细胞毒作用,但似乎不具备 CAR-T 细胞相关副作用。CAR-NK 细胞因此是癌症免疫治疗的潜在优良候选者。然而,其应用受到重大挑战限制,尤其是 CAR-NK 细胞在体内持久性有限,这阻碍其持续发挥抗癌作用。基于以上背景,本综述讨论 CAR-T 和 CAR-NK 细胞治疗血液系统恶性肿瘤的现状和应用,并比较这两类基因修饰免疫细胞的结构、遗传学和临床结局。
In recent years, following the groundbreaking achievements of chimeric antigen receptor (CAR) T cell therapy in hematological cancers, and advancements in cell engineering technologies, the exploration of other immune cells has garnered significant attention. CAR-Therapy extended beyond T cells to include CAR natural killer (NK) cells and CAR-macrophages, which are firmly established in the clinical trial landscape. Less conventional immune cells are also making their way into the scene, such as CAR mucosal-associated invariant T (MAIT) cells. This progress is advancing precision medicine and facilitating the development of ready-to-use biological treatments. However, in view of the unique features of natural killer cells, adoptive NK cell immunotherapy has emerged as a universal, allogenic, "off-the shelf" therapeutic strategy. CAR-NK cytotoxic cells present targeted tumor specificity but seem to be devoid of the side effects associated with CAR-T cells. CAR-NK cells appear to be potentially promising candidates for cancer immunotherapy. However, their application is hindered by significant challenges, particularly the limited persistence of CAR-NK cells in the body, which poses a hurdle to their sustained effectiveness in treating cancer. Based upon the foregoing, this review discusses the current status and applications of both CAR-T cells and CAR-NK cells in hematological cancers, and provides a comparative analysis of the structure, genetics, and clinical outcomes between these two types of genetically modified immune cells.
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