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 Race of CAR Therapies: CAR-NK Cells for Fighting B-Cell Hematological Cancers.
诸如化疗等标准疗法仅对 40% 的成人 ALL 患者有效并达到五年生存率,因此需要采用新的替代方案,例如靶向恶性细胞特定受体的免疫治疗。
急性淋巴细胞白血病(ALL)和慢性淋巴细胞白血病(CLL)分别是儿童和老年人最常见的白血病。标准疗法如化疗,在成人ALL患者中仅有40%能达到五年生存,因此需要采用新方案,例如靶向恶性细胞特定受体的免疫疗法。在所有治疗选择中,CAR(嵌合抗原受体)疗法已成为复发或难治性血液系统癌症患者的新机遇。CAR最初设计为与T淋巴细胞结合形成CAR-T细胞,其结果令人鼓舞,现已作为药物投入使用。然而,CAR-T细胞的副作用,以及无法在不引起移植物抗宿主病的情况下输注异基因CAR-T产品,促使研究者寻找其他细胞来源来解决这些问题,例如自然杀伤(NK)细胞。虽然CAR治疗是一场由CAR-T细胞领跑的高速竞赛,CAR-NK细胞也正逐步(但稳步地)巩固其地位;其已显示的疗效及缺乏不良副作用,为CAR治疗打开了新的大门。CAR-NK如今已成为这一领域的重要组成部分。
Acute lymphoblastic leukemia (ALL) and Chronic lymphocytic leukemia (CLL) are the most common leukemias in children and elderly people, respectively. Standard therapies, such as chemotherapy, are only effective in 40% of ALL adult patients with a five-year survival rate and therefore new alternatives need to be used, such as immunotherapy targeting specific receptors of malignant cells. Among all the options, CAR (Chimeric antigen receptor)-based therapy has arisen as a new opportunity for refractory or relapsed hematological cancer patients. CARs were designed to be used along with T lymphocytes, creating CAR-T cells, but they are presenting such encouraging results that they are already in use as drugs. Nonetheless, their side-effects and the fact that it is not possible to infuse an allogenic CAR-T product without causing graft-versus-host-disease, have meant using a different cell source to solve these problems, such as Natural Killer (NK) cells. Although CAR-based treatment is a high-speed race led by CAR-T cells, CAR-NK cells are slowly (but surely) consolidating their position; their demonstrated efficacy and the lack of undesirable side-effects is opening a new door for CAR-based treatments. CAR-NKs are now in the field to stay.
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