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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR-NK cells from engineered pluripotent stem cells: Off-the-shelf therapeutics for all patients.
CAR-NK cells from engineered pluripotent stem cells: Off-the-shelf therapeutics for all patients.
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以嵌合抗原受体(CAR)T细胞过继性细胞疗法治疗血液系统恶性肿瘤的临床成功,彻底改变了细胞免疫治疗领域。然而,由于使用自体T细胞的性质,除了与CAR-T 疗法优化相关的科学挑战外,可负担性和可及性是主要障碍。自然杀伤(NK)细胞是一种特化的免疫效应细胞类型,能够在不受人类白细胞抗原(HLA)限制且无需预先致敏的情况下识别并杀伤靶细胞。CAR-NK细胞不会引起移植物抗宿主病,并且可以从无关供者以及多能干细胞(PSC)中获得,代表了一种理想的现货型治疗产品,可随时用于患者。
此外,与细胞毒性T细胞不同,NK细胞特异性靶向并清除癌症干细胞,而癌症干细胞正是导致复发和转移的细胞。PSC可以在多能阶段通过CAR进行基因操作和工程改造,从而能够建立永久、稳定且克隆化的PSC-CAR细胞系,用于制造无限量的同质性CAR-NK细胞。针对癌症、病毒感染和自身免疫性疾病多种抗原的多个主PSC-CAR细胞库,为所有患者提供了取之不尽的细胞来源。用于PSC扩增和NK细胞生产的下一代3D生物反应器平台的开发,克服了与CAR-NK产品成本和可扩展性相关的主要障碍。
Clinical success of adoptive cell therapy with chimeric antigen receptor (CAR) T cells for treating hematological malignancies has revolutionized the field of cellular immunotherapy.
However, due to the nature of utilizing autologous T cells, affordability and availability are major hurdles, in addition to scientific challenges relating to CAR-T therapy optimization. Natural killer (NK) cell is a specialized immune effector cell type that recognizes and kills targets without human leukocyte antigen (HLA) restriction and prior sensitization.
CAR-NK cells do not cause graft vs host disease and can be obtained from unrelated donors as well as pluripotent stem cells (PSC), representing an ideal off-the-shelf therapeutics readily available for patients.
Furthermore, unlike cytotoxic T cells, NK cells specifically target and eliminate cancer stem cells, which are the cells causing relapse and metastasis. PSCs can be genetically manipulated and engineered with CARs at the pluripotent stage, which allows the establishment of permanent, stable, and clonal PSC-CAR lines for the manufacture of unlimited homogenous CAR-NK cells.
Multiple master PSC-CAR cell banks targeting a variety of antigens for cancer, viral infection, and autoimmune diseases provide inexhaustible cell sources for all patients. Development of a next-generation 3D bioreactor platform for PSC expansion and NK cell production overcomes major barriers related to cost and scalability for CAR-NK product.
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