CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Worked to the bone: antibody-based conditioning as the future of transplant biology.
Worked to the bone: antibody-based conditioning as the future of transplant biology.
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在造血干细胞移植前对骨髓进行预处理对于根除疾病的主要原因、促进供体细胞植入以及通过免疫抑制避免移植排斥至关重要。标准预处理方案通常包括化疗和/或放疗,已被证明在清除骨髓方面是成功的,但也与严重毒性和高发生率的治疗相关死亡率相关。基于抗体的预处理是一个发展中的领域,迄今为止,在实验模型中大多显示出改善的毒性特征,并且与传统预处理相比改善了移植结果。大多数基于抗体的预处理疗法涉及单克隆/裸抗体,例如用于移植物抗宿主病预防的阿仑单抗和用于EB病毒预防的利妥昔单抗,这两种药物均处于纳入预处理方案的II期试验中。尽管如此,包括抗体-药物偶联物、放射性标记抗体和CAR-T 细胞在内的替代免疫疗法在预处理环境中显示出前景。在此,我们分析基于抗体的药物在移植前预处理方案中的现状,并评估其在移植生物学未来中的潜力。
Conditioning of the bone marrow prior to haematopoietic stem cell transplant is essential in eradicating the primary cause of disease, facilitating donor cell engraftment and avoiding transplant rejection via immunosuppression. Standard conditioning regimens, typically comprising chemotherapy and/or radiotherapy, have proven successful in bone marrow clearance but are also associated with severe toxicities and high incidence of treatment-related mortality.
Antibody-based conditioning is a developing field which, thus far, has largely shown an improved toxicity profile in experimental models and improved transplant outcomes, compared to traditional conditioning.
Most antibody-based conditioning therapies involve monoclonal/naked antibodies, such as alemtuzumab for graft-versus-host disease prophylaxis and rituximab for Epstein-Barr virus prophylaxis, which are both in Phase II trials for inclusion in conditioning regimens. Nevertheless, alternative immune-based therapies, including antibody-drug conjugates, radio-labelled antibodies and CAR-T cells, are showing promise in a conditioning setting.
Here, we analyse the current status of antibody-based drugs in pre-transplant conditioning regimens and assess their potential in the future of transplant biology.
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