为癌症免疫治疗设计自然杀伤细胞的输送技术
Delivery technologies to engineer natural killer cells for cancer immunotherapy
原文发布日期:2021-04-22
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In recent years, immune cell-based cancer therapeutics have been utilized broadly in the clinic. Through advances in cellular engineering, chimeric antigen receptor (CAR) T-cell therapies have demonstrated substantial success in treating hematological tumors and have become the most prominent cell-based therapy with three commercialized products in the market. However, T-cell-based immunotherapies have certain limitations, including a restriction to autologous cell sources to avoid severe side-effects caused by human leukocyte antigen (HLA) mismatch. This necessity for personalized treatment inevitably results in tremendous manufacturing and time costs, reducing accessibility for many patients. As an alternative strategy, natural killer (NK) cells have emerged as potential candidates for improved cell-based immunotherapies. NK cells are capable of killing cancer cells directly without requiring HLA matching. Furthermore, NK cell-based therapies can use various allogeneic cell sources, allowing for the possibility of “off-the-shelf” immunotherapies with reduced side-effects and shortened manufacturing times. Here we provide an overview of the use of NK cells in cancer immunotherapy, their current status in clinical trials, as well as the design and implementation of delivery technologies—including viral, non-viral, and nanoparticle-based approaches—for engineering NK cell-based immunotherapies.
近年来,基于免疫细胞的癌症治疗手段已在临床得到广泛应用。随着细胞工程技术的进步,嵌合抗原受体(CAR)T细胞疗法在治疗血液肿瘤方面取得显著成效,已成为最突出的细胞治疗方法,目前已有三种商业化产品上市。然而,基于T细胞的免疫疗法存在一定局限性,包括必须使用自体细胞来源以避免人类白细胞抗原(HLA)不匹配引发的严重副作用。这种个性化治疗的需求不可避免地导致巨大的生产成本和时间成本,降低了多数患者的可及性。作为一种替代策略,自然杀伤(NK)细胞已成为改进细胞免疫疗法的潜在候选者。NK细胞能够直接杀伤癌细胞且无需HLA配型。此外,基于NK细胞的疗法可采用多种异体细胞来源,为实现"即用型"免疫疗法提供了可能,这种疗法不仅副作用更小,还能缩短生产时间。本文概述了NK细胞在癌症免疫治疗中的应用、临床试验现状,以及用于开发NK细胞免疫疗法的递送技术(包括病毒载体、非病毒载体和纳米颗粒方法)的设计与实施。
Delivery technologies to engineer natural killer cells for cancer immunotherapy
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